bioRxiv Science⌕ Search

Biology subjects

Yu, D.

Publications and source records attributed to Yu, D..

At least 163 records · Page 9Linked to original sources
bioRxiv2019

The transcription factor Shox2 shapes thalamocortical neuron firing properties by regulation of key ion channels

Thalamocortical neurons (TCNs) transmit information about sensory stimuli from the thalamus to the cortex. In response to different physiological states and demands TCNs can fire in tonic and/or phasic burst modes. These firing properties of TCNs are supported by precisely timed inhibitory synaptic inputs from the thalamic reticular nucleus and intrinsic currents, including T-type Ca2+ and HCN currents. These intrinsic currents are mediated by Cav3.1 and HCN channel subunits, and alterations in expression or modulation of these channels can have dramatic implications on thalamus function. The factors that regulate these currents controlling the firing patterns important for integration of the sensory stimuli and the consequences resulting from the disruption of these firing patterns are not well understood. Shox2 is a transcription factor known to be important for pacemaker activity in the heart. We show here that Shox2 is also expressed in adult mouse thalamus. We hypothesized that genes regulated by Shox2s transcriptional activity may be important for physiological properties of TCNs. In this study, we used RNA sequencing on control and Shox2 knockout mice to determine Shox2-affected genes and revealed a network of ion channel genes important for neuronal firing properties. Quantitative PCR confirmed that expression of Hcn2, 4 and Cav3.1 genes were affected by Shox2 KO. Western blotting showed expression of the proteins for these channels was decreased in the thalamus, and electrophysiological recordings showed that Shox2 KO impacted the firing and synaptic properties of TCNs. Finally, behavioral studies revealed that Shox2 expression in TCNs play a role in somatosensory function and object recognition memory. Overall, these results reveal Shox2 as a transcription factor important for TCN firing properties and thalamic function.

neuroscience↗
bioRxiv2019

Interaction between DNA damage response, translation and apoptosome determines cancer susceptibility to TOP2 poisons

Topoisomerase II poisons are one of the most common class of chemotherapeutics used in cancer. We show that glioblastoma (GBM), the most malignant of all primary brain tumors in adults is responsive to TOP2 poisons. To identify genes that confer susceptibility to this drug in gliomas, we performed a genome-scale CRISPR knockout screen with etoposide. Genes involved in protein synthesis and DNA damage were implicated in etoposide susceptibility. To define potential biomarkers for TOP2 poisons, CRISPR hits were overlapped with genes whose expression correlates with susceptibility to this drug across glioma cell lines, revealing ribosomal protein subunit RPS11, 16, 18 as putative biomarkers for response to TOP2 poisons. Loss of RPS11 impaired the induction of pro-apoptotic gene APAF1 following etoposide treatment, and led to resistance to this drug and doxorubicin. The expression of these ribosomal subunits was also associated with susceptibility to TOP2 poisons across cell lines from multiple cancers.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC=\"FIGDIR/small/614024v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (14K):\norg.highwire.dtl.DTLVardef@310f7org.highwire.dtl.DTLVardef@14ed578org.highwire.dtl.DTLVardef@a0d9c0org.highwire.dtl.DTLVardef@37f59a_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer 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↗
bioRxiv2019

Genetic overlap between obsessive-compulsive disorder, related symptoms in the population and insulin signaling: etiological implications

ObjectiveObsessive-compulsive symptoms (OCS) in the population have been linked to obsessive-compulsive disorder (OCD) in genetic and epidemiological studies. Insulin signaling has been implicated in OCD. We extend previous work by assessing genetic overlap between OCD, population-based OCS, and central nervous system (CNS) and peripheral insulin signaling.\n\nMethodsWe conducted genome-wide association studies (GWASs) in the population-based Philadelphia Neurodevelopmental Cohort (PNC, 650 children and adolescents) of the total OCS score and six OCS factors from an exploratory factor analysis of 22 questions. Subsequently, we performed polygenic risk score (PRS) analysis to assess shared genetic etiologies between clinical OCD (using GWAS data from the Psychiatric Genomics Consortium), the total OCS score and OCS factors. We then performed gene-set analyses with a set of OCD-linked genes centered around CNS insulin-regulated synaptic function and PRS analyses for five peripheral insulin signaling-related traits. For validation purposes, we explored data from the independent Spit for Science population cohort (5047 children and adolescents).\n\nResultsIn the PNC, we found a shared genetic etiology between OCD and impairment, contamination/cleaning and guilty taboo thoughts. In the Spit for Science cohort, we were able to validate the finding for contamination/cleaning, and additionally observed genetic sharing between OCD and symmetry/counting/ordering. The CNS insulin-linked gene-set associated with symmetry/counting/ordering. We also identified genetic sharing between peripheral insulin signaling-related traits (type 2 diabetes and the blood levels of HbA1C, fasting insulin and 2 hour glucose) and OCD as well as certain OCS.\n\nConclusionsOCD, OCS in the population and insulin-related traits share genetic risk factors, indicating a common etiological mechanism underlying somatic and psychiatric disorders.

genetics↗
bioRxiv2019

The Life History of Human Foraging: Cross-Cultural and Individual Variation

Human adaptation depends upon the integration of slow life history, complex production skills, and extensive sociality. Refining and testing models of the evolution of human life history and cultural learning will benefit from increasingly accurate measurement of knowledge, skills, and rates of production with age. We pursue this goal by inferring individual hunters of hunting skill gain and loss from approximately 23,000 hunting records generated by more than 1,800 individuals at 40 locations. The model provides an improved picture of ages of peak productivity as well as variation within and among ages. The data reveal an average age of peak productivity between 30 and 35 years of age, though high skill is maintained throughout much of adulthood. In addition, there is substantial variation both among individuals and sites. Within study sites, variation among individuals depends more upon heterogeneity in rates of decline than in rates of increase. This analysis sharpens questions about the co-evolution of human life history and cultural adaptation. It also demonstrates new statistical algorithms and models that expand the potential inferences drawn from detailed quantitative data collected in the field.

animal behavior and cognition↗
bioRxiv2019

SPIKEPIPE: A metagenomic pipeline for the accurate quantification of eukaryotic species occurrences and abundances using DNA barcodes or mitogenomes

The accurate quantification of eukaryotic species abundances from bulk samples remains a key challenge for community description and environmental biomonitoring. We resolve this challenge by combining shotgun sequencing, mapping to reference DNA barcodes or to mitogenomes, and three correction factors: (1) a percent-coverage threshold to filter out false positives, (2) an internal-standard DNA spike-in to correct for stochasticity during sequencing, and (3) technical replicates to correct for stochasticity across sequencing runs. This pipeline achieves a strikingly high accuracy of intraspecific abundance estimates from samples of known composition (mapping to barcodes R2=0.93, mitogenomes R2=0.95) and a high repeatability across environmental-sample replicates (barcodes R2=0.94, mitogenomes R2=0.93). As proof of concept, we sequence arthropod samples from the High Arctic systematically collected over 17 years, detecting changes in species richness, abundance, and phenology using either barcodes or mitogenomes. SPIKEPIPE provides cost-efficient and reliable quantification of eukaryotic communities, with direct application to environmental biomonitoring. Statement of authorshipNMS has been involved in running the BioBasis sampling program for more than twenty years. TR, NMS, DWY, and OO conceived the study and its design. TH led the work in generating all the DNA samples and YJ led the work in assembling and annotating the mitogenomes for the mitochondrial genome reference database. TH led the work in generating the mock communities and bulk samples, with contributions from YJ and JW. YJ and DWY developed the molecular and bioinformatic methods. OO led the modelling of the data. TR and OO wrote the first draft of the manuscript, and all authors contributed substantially to its further improvement. Data accessibility statementShould the manuscript be accepted, the data supporting the results will be archived in an appropriate public repository (Dryad), and the data DOI will be included at the end of the article. The bioinformatic and R scripts and associated data tables will also be made available on github.com.

ecology↗
bioRxiv2019

Genome wide meta-analysis identifies genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders.

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed a meta-analysis of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders identifying three groups of inter-related disorders. We detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning in the second trimester prenatally, and play prominent roles in a suite of neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

genomics↗
bioRxiv2018

Efficient assembly and long-term stability of defensive microbiomes via private resources and community bistability

Understanding the mechanisms promoting the assembly and maintenance of host-beneficial microbiomes is an open problem. An increasing amount of evidence supports the idea that animal and plant hosts can use private resources and the ecological phenomenon known as community bistability to favour some microbial strains over others. We briefly review empirical evidence showing that hosts can: (i) protect the growth of beneficial strains in an isolated habitat, (ii) use antibiotic compounds to suppress non-beneficial, competitor strains, and (iii) provide resources (for a limited time) that only beneficial strains are able to translate into an increased rate of growth, reproduction, or antibiotic production. We then demonstrate in a spatially explicit, individual-based model that these three mechanisms act similarly by selectively promoting the initial proliferation of preferred strains, that is, by acting as a private resource. By explicitly modelling localized microbial interactions and diffusion dynamics, we further show that an intermediate level of antibiotic diffusion is the most efficient mechanism in promoting preferred strains and that that there is a wide range of conditions under which hosts can promote the assembly of a self-sustaining defensive microbiome. This, in turn, supports the idea that hosts readily evolve to promote host-beneficial defensive microbiomes.

microbiology↗
bioRxiv2018

The biodiversity benefit of native forest over Grain-for-Green plantations

AimChinas Grain-for-Green Program (GFGP) is the largest reforestation program in the world and has been operating since 1999. The GFGP has promoted the establishment of tree plantations over the preservation of diverse native forest. In a previous study (Hua et al. 2016, Nat Comms 7:12717), we showed that native forest supports higher species richnesses of birds and bees than do GFGP plantations. We also showed that mixed-plantation GFGP plantations, which are mostly made up of two to five neighboring monoculture stands of different tree species, planted in checkboard fashion, support a level of bird (but not bee) species richness that is higher than any of the individual GFGP monocultures, although still below that of native forest. To better protect terrestrial biodiversity, which is an important objective of Chinas land-sustainability spending, we recommended that the GFGP should firstly prioritize native forest conservation and regeneration and secondly promote checkerboard planting arrangements over monocultures. Here, we use metabarcoding of arthropod biodiversity to test the generality of these results and policy recommendations.\n\nLocationSichuan, China\n\nMethodsWe used COI-amplicon sequencing ( metabarcoding) of bulk samples of arthropods that were collected with pan traps in native forest, cropland, mixed plantations, and monocultures.\n\nResultsNative forest supports the highest overall levels of arthropod species richness and diversity, followed by cropland and mixed plantations, followed by bamboo monoculture, followed by the other monocultures. Also, the arthropod community in mixed plantations shares more species with native forest than do any of the monocultures. Together, these results show a biodiversity value of mixed plantations for arthropods that is higher than that previously indicated by bees alone.\n\nMain conclusionThese results strengthen our original policy recommendations of (1) promoting the conservation and expansion of native forest and (2) promoting mixed-plantation arrangements. The value of this added metabarcoding-based analysis is that these policy prescriptions are now also based on a dataset that includes over 500 species-resolution taxa, ranging across the Arthropoda.

ecology↗
bioRxiv2018

Novel Data Transformations for RNA-seq Data Analysis

We propose eight data transformations for RNA-seq data analysis aiming to make the transformed sample mean to be representative of the distribution center since it is not always possible to transform count data to satisfy the normality assumption. Simulation studies showed that limma based on transformed data by using the rv transformation (denoted as limma+rv) performed best compared with limma based on transformed data by using other transformation methods in term of high accuracy and low FNR, while keeping FDR at the nominal level. For large sample size, limma based on transformed data by using the 8 proposed transformation methods had similar performance to limma based on transformed data by using existing transformation methods for equal library size scenarios. Otherwise, limma based on transformed data by using the rv, lv, rv2, or lv2 transformation, or by using the existing voom transformation performed better than limma based on data from other transformation methods. Real data analysis results showed that limma+ l2 performed best, while limma+ rv also had good performance.

bioinformatics↗
bioRxiv2018

GWAS using 2b-RAD sequencing identified three mastitis important SNPs via two-stage association analysis in Chinese Holstein cows.

BackgroundBovine mastitis is a key disease restricting developing global dairy industry. Genomic wide association studies (GWAS) provided a convenient way to understand the biological basis of mastitis and better prevent or treat the disease. 2b-RADseq is a reduced-representation sequencing that offered a powerful method for genome-wide genetic marker development and genotyping. This study, GWAS using two-stage association analysis identified mastitis important genes single nucleotide polymorphisms (SNP) in Chinese Holstein cows.\n\nResultsIn the selected Chinese Holstein cows population, we identified 10,058 SNPs and predicted their allele frequencies. In stage I, 42 significant SNPs screened out in Chinese Holstein cows via Bayesian (P<0.001), while logistic regression model identified 51 SNPs (P<0.01). Twenty-seven significant SNPs appeared simultaneously in both analytical models, which of them only three significant SNPs (rs75762330, C>T, PIC=0.2999; rs88640083, A>G, PIC=0.1676; rs20438858, G>A, PIC=0.3366) located in non-coding region (introns and intergenic) screened out associated with inflammation or immune response. GO enrichment analysis showed that they annotated to three genes (PTK2B, SYK and TNFRSF21), respectively. Stage II? case-control study used to verify three important SNPs associated with dairy cows mastitis traits in independent population. Data suggested that the correlation between these three SNPs (rs75762330, P<0.025; rs88640083, P<0.005; rs20438858, P<0.001) and mastitis traits in dairy cows were consistent with stage I.\n\nConclusionTwo-stage association analysis approved that three significant SNPs associated with mastitis traits in Chinese Holstein cows. Gene function analysis indicated that three genes (PTK2B, SYK and TNFRSF21) involved in inflammation and immune response of dairy cows. Suggesting that they as new candidate genes have an impact on mastitis susceptibility (PTK2B and SYK, OR>1) or resistance (TNFRSF21, OR<1) in Chinese Holstein cows.

genomics↗
bioRxiv2018

New Statistical Methods for Constructing Robust Differential Correlation Networks

The interplay among microRNAs (miRNAs) plays an important role in the developments of complex human diseases. Co-expression networks can characterize the interactions among miRNAs. Differential correlation network is a powerful tool to investigate the differences of co-expression networks between cases and controls. To construct a differential correlation network, the Fishers Z-transformation test is usually used. However, the Fishers Z-transformation test requires the normality assumption, the violation of which would result in inflated Type I error rate. Several bootstrapping-based improvements for Fishers Z test have been proposed. However, these methods are too computationally intensive to be used to construct differential correlation networks for high-throughput genomic data. In this article, we proposed six novel robust equal-correlation tests that are computationally efficient. The systematic simulation studies and a real microRNA data analysis showed that one of the six proposed tests (ST5) overall performed better than other methods.

bioinformatics↗
bioRxiv2018

Experimental demonstration that screening can enable the environmental recruitment of a defensive microbiome

Many animals and plants recruit beneficial microbes from the environment, enhancing their defence against pathogens. However, we have only a limited understanding of the assembly mechanisms involved. A game-theoretical concept from economics, screening, potentially explains how a host selectively recruits mutualistic microbes from the environment by fomenting and biasing competition among potential symbionts in such a way that the more likely winners are antibiotic producers. The cuticular microbiomes of Acromyrmex leaf-cutting ants inspired one of the first applications of screening theory, and here we simulate this system in vitro to test screening. On agar infused with antibacterial metabolites from Acromyrmexs vertically transmitted Pseudonocardia bacteria, we show that antibiotic-producing Streptomyces bacteria exhibit higher growth rates than do non-antibiotic-producer strains and are more likely to win in direct competition. Our results demonstrate how game-theoretical concepts can provide powerful insight into host-microbiome coevolution.

evolutionary biology↗
bioRxiv2018

Insight into relationship between micro-consortia, nitrogen source and petroleum degradation at low temperature anaerobic condition

Biostimulation by addition nutrients has been proved to be an effective bioremediation strategies. Revealing response law of nitrogen source and structure characteristics of anaerobic petroleum degrading microorganisms microbial population will help us optimize nutrient to promote oil degradation. Anaerobic micro-consortia characteristics in the enrichment marine sediment samples with different nitrogen source, combining with analysis of the oil degradation rates were studied in this paper, as well as functional genes involved in petroleum degradation were also analyzed. On the basis of optimizing the best inorganic nitrogen sources and organic nitrogen sources, an effective medium was designed by response surface methodology that used for enriching petroleum degradation micro-consortia. Amplicon sequencing analysis showed that the population of microorganisms migrated obviously when enriched with different nitrogen sources. With the increase of oil degradation rate, the microbial diversity was significantly decreased, and concentrated on a limited number of genera. The reasonable proportions of GammaProteobacteria, Bacteroidetes and Fusobacteria made the greatest contribution to petroleum degradation. Metagenomic analysis unveiled the mixed nitrogen source promoted the expression of functional genes related to petroleum degradation such as the transfer of succinyl-CoA, synthesis of acetyl CoA and {beta}-oxidation cycle, and was beneficial to degradation of petroleum at low temperature anaerobic condition.\n\nOriginality Significance StatementAddition of nutrients can promote growth of indigenous petroleum degradation-related bacteria and be helpful to the rapid degradation of petroleum. Previous studies accurately characterized aerobic microorganisms on petroleum degradation. However, we still known little about anaerobic microorganisms in marine environment. Most biostimulation methods use inorganic salt as the main nutritional supplement to improve the efficiency of petroleum degradation, but effects of different nitrogen sources on diversity of microorganisms and distribution of functional genes related to petroleum degradation at anaerobic conditions are still unknown. In this research, the effects of nitrogen on petroleum biodegradation, anaerobic microconsortium structure and distribution of genes related to petroleum degradation were unveiled by using amplicon sequencing and metagenomic analysis.

microbiology↗
bioRxiv2018

PRL-1 is required for neuroprotection against olfactory CO2 stimulation in Drosophila

The Mammalian phosphatase of regenerating liver (PRL) family is primarily recognized for its oncogenic properties. Here we found that in Drosophila, loss of prl-1 resulted in CO2-induced brain disorder presented as irreversible wing hold up with enhancement of Ca2+ responses at the neuron synaptic terminals. Overexpression of Prl-1 in the nervous system could rescue the mutant phenotype. We show that Prl-1 is particularly expressed in CO2-responsive neural circuit and the higher brain centers. Ablation of the CO2 olfactory receptor, Gr21a, suppressed the mutant phenotype, suggesting that CO2 acts as a neuropathological substrate in absence of Prl-1. Further studies found that the wing hold up is an obvious consequence upon knockdown of Uex, a magnesium transporter, which directly interacts with Prl-1. Conditional expression of Uex in the nervous system could rescue the phenotype of prl-1 mutants. We demonstrate that Uex acts genetically downstream of Prl-1. Our findings provide important insights into mechanisms of Prl-1 protection against olfactory CO2 stimulation induced brain disorder at the level of detailed neural circuits and functional molecular connections.

neuroscience↗
bioRxiv2018

Transcriptome Profiling Reveals Inhibitory Effect of Down-regulated ZBTB38 gene on the Transcriptional Regulation of Tumor Cells Proliferation

Transcription factor ZBTB38 belongs to the zinc finger protein family and contains the typical BTB domains. Only several predicted BTB domain-containing proteins encoded in the human genome have been functionally characterized. No relevant studies have been reported concerning the effect of down-regulated ZBTB38 gene expression on tumor cells through transcriptome analysis. In the present study, 2,438 differentially expressed genes in ZBTB38-/- SH-SY5Y cells were obtained via high-throughput transcriptome sequencing analysis, 83.5% of which was down-regulated. Furthermore, GO functional clustering and KEGG pathway enrichment analysis of these differentially expressed genes (DEGs) revealed that the knocked-down transcription factor ZBTB38 interacted with p53 and arrested cell cycles to inhibit the proliferation of the tumor cells. Besides, it also significantly down-regulated the expressions of PTEN, a \"molecular switch\" of the PI3K/Akt signaling pathway, and RB1CC1, the key gene for autophagy initiation, and blocked autophagy to accelerate the apoptosis of tumor cells. ZBTB38-/- SH-SY5Y cells were investigated at the whole transcriptome level and key DEGs were screened in the present study for the first time, providing a theoretical foundation for exploring the molecular mechanism of inhibition of tumor cell proliferation and targeted anti-tumor therapies.

genomics↗
bioRxiv2018

Establishment and Application of a duplex real-time qPCR method for detection of Salmonella spp. and Serratia fonticola in imported feedstuffs

Salmonella spp. is a high-risk bacterial pathogen that is monitored in imported animal-derived feedstuffs. Serratia fonticola is the bacterial species most frequently confused with Salmonella spp. in traditional identification methods based on biochemical characteristics, which are time-consuming and labor-intensive, and thus unsuitable for daily inspection and quarantine work. In this study, we established a duplex real-time qPCR method with invA-and gyrB-specific primers and probes corresponding to Salmonella spp. and S. fonticola. The method could simultaneously detect both pathogens in imported feedstuffs, with a minimum limit of detection for Salmonella spp. and S. fonticola of 197 copies/L and 145 copies/L, respectively (correlation coefficient R2 = 0.999 in both cases). The amplification efficiency for Salmonella spp. and S. fonticola was 98.346% and 96.49%, respectively. Detection of clinical samples was consistent with method GB/T 13091-2002, and all 20 artificially contaminated imported feed samples were positively identified. Thus, the developed duplex real-time qPCR assay displays high specificity and sensitivity, and can be used for the rapid and accurate detection of genomic DNA from Salmonella spp. and S. fonticola within hours. This represents a significant improvement in the efficiency of detection of both pathogens in imported feedstuffs.\n\nImportanceImported feedstuffs must be tested for pathogenic Salmonella species that represent a biological hazard. Various non-Salmonella colony-forming species belong to Enterobacteriaceae, and Serratia fonticola forms colonies of similar color and morphology to Salmonella spp., leading to confusion in daily quarantine tests. Traditional methods based on biochemical and serological characteristics are cumbersome and labor-intensive, and unable to fully support current quarantine testing demands. Thus, there is an urgent need to develop a rapid and accurate method for the effective identification of these pathogens. The duplex real-time qPCR method established herein can rapidly identify Salmonella spp. and S. fonticola, and has great potential for application to feed safety and prevention of exterior pathogens.

microbiology↗