Biology subjects

Hu, Y.

Publications and source records attributed to Hu, Y..

At least 613 records · Page 34Linked to original sources

bioRxiv2019

Uncovering the microbiome of invasive sympatric European brown hares and European rabbits in Australia

European brown hares (Lepus europaeus) and European rabbits (Oryctolagus cuniculus) are invasive pest species in Australia, with rabbits having a substantially larger environmental impact than hares. As their spatial distribution in Australia partially overlaps, we conducted a comparative microbiome study to determine how the composition of the gastrointestinal microbiota varies between these species, since this may indicate species differences in diet, physiology, and other internal and external factors. We analysed the faecal microbiome of wild hares and rabbits from a sympatric environment, additionally comparing Illumina and Nanopore sequencing platforms. The faecal microbiomes varied significantly between hares and rabbits, despite both species occupying a similar habitat. Moreover, we identified significantly more variation in faecal microbiome composition between individual rabbits compared to hares. The faecal microbiome in both species was dominated by the phyla Firmicutes and Bacteroidetes, typical of many vertebrates. Many phyla, including Actinobacteria, Proteobacteria, and Patescibacteria, were shared between rabbits and hares. In contrast, bacteria from phylum Verrucomicrobia were present only in rabbits, while phyla Lentisphaerae and Synergistetes were represented only in hares. We did not identify phylum Spirochetes in Australian hares; this phylum was previously shown to be present at high relative abundance in European hare faecal samples. These differences in the faecal microbiota between hares and rabbits in Australia may be associated with differences in diet, and potentially behaviour, of the host species in their non-native range, which may influence the environmental impacts that these species have in Australia.

ecology↗

bioRxiv2019

Prevalence of beta-lactam drug-resistance genes in commensal Escherichia coli contaminating ready-to-eat lettuce

The objective of this study was to evaluate the prevalence of antibiotic resistance and beta-lactam drug resistance genes in Escherichia coli isolated from ready-to-eat lettuce, obtained from local supermarkets in Northern California. Bags of lettuce were purchased from 4 chain supermarkets during three different periods--Oct 2018-Jan 2019, Feb 2019-Apr 2019 and May 2019-July 2019. From 91 packages of lettuce, we recovered 34 E. coli isolates from 22 (24%) lettuce samples. All E. coli isolates were genotyped by multilocus sequence typing (MLST), and we found 15 distinct sequence types (STs). Five of these genotypes (ST2819, ST4600, ST2432, ST1198 and ST5143) have been reported to cause infection in humans. Twenty (59%) E. coli isolates were found resistant to at least one of the antibacterial drugs. They included resistance to ampicillin (AMP, 85%) and ampicillin/sulbactam (SAM, 50%), cefoxitin (FOX, 40%) and cefuroxime (CXM, 35%). We found 8 (40%) of 20 beta-lactam resistant E. coli isolates to carry blaCTX-M; 5 (25%) tested positive for blaSHV, while only 4 (20%) tested positive for blaTEM. Additionally, we identified a class A broad-spectrum beta-lactamase SED-1 gene, blaSED, reported by others in Citrobacter sedlakii isolated from bile of a patient. This study found that a large proportion of fresh lettuce carry beta-lactam drug-resistant E. coli, which could serve as a reservoir for drug resistance genes that could potentially enter pathogens to cause human infections.

microbiology↗

bioRxiv2019

Precise regulation of the relative rates of surface area and volume synthesis in dynamic environments

Bacterial cells constantly face complex environmental changes in their natural habitats. While steady-state cell size correlates with nutrient-determined growth rate, it remains unclear how cells regulate their morphology during rapid environmental changes. Here, we systematically quantified cellular dimensions throughout passage cycles of stationary-phase cells diluted into fresh medium and grown back to saturation, and found that cells exhibit characteristic dynamics in surface area to volume ratio (SA/V). SA/V dynamics were conserved across many genetic/chemical perturbations, as well as across species and growth temperatures. We developed a model with a single fitting parameter, the time delay between surface and volume synthesis, that quantitatively explained our SA/V observations, and showed that the time delay was indeed due to differential expression of volume and surface-related genes. The first division after dilution occurred at a tightly controlled SA/V, a previously unrecognized size-control mechanism highlighting the relevance of SA/V. Finally, our time-delay model successfully predicted the quantitative changes in SA/V dynamics due to altered surface area synthesis rates or time delays from translation inhibition. Our minimal model thus provides insight into how cells regulate their morphologies through differential regulation of surface area and volume synthesis and potentiates deep understanding of the connections between growth rate and cell shape in complex environments.

microbiology↗

bioRxiv2019

Synergistic effect: a common theme in mixed-species litter decomposition

O_LILitter decomposition plays a key role in ecosystem nutrients cycling, yet, to date science is lacking a comprehensive understanding of the non-additive effect in mixing litter decomposition.\nC_LIO_LIIn order to fill that gap, we compiled 69 individual studies for the purpose of performing two sub-meta-analyses on the non-additive effect.\nC_LIO_LIOur results show that a significantly synergistic effect occurs at global scale with the average increase by 2-4% in litter mixture decomposition; In particular, low-quality litter in mixture shows a significantly synergistic effect, while no significant change is observed with high-quality species. Additionally, the synergistic effect turns into the antagonistic effect when soil fauna is absent or litter decomposition enters into humus-near stage. In contrast to temperate and tropical areas, studies in frigid area also show a significantly antagonistic effect.\nC_LIO_LIOur meta-analysis provides a systematic evaluation of the non-additive effect in decomposition mixed litters, which is critical for understanding and improving the carbon forecasts and nutrient dynamics.\nC_LI

ecology↗

bioRxiv2019

Predicting cellular position in the Drosophila embryo from Single-Cell Transcriptomics data

Single-cell RNA-seq technologies are rapidly evolving but while very informative, in standard scRNAseq experiments the spatial organization of the cells in the tissue of origin is lost. Conversely, spatial RNA-seq technologies designed to keep the localization of the cells have limited throughput and gene coverage. Mapping scRNAseq to genes with spatial information increases coverage while providing spatial location. However, methods to perform such mapping have not yet been benchmarked. To bridge the gap, we organized the DREAM Single-Cell Transcriptomics challenge focused on the spatial reconstruction of cells from the Drosophila embryo from scRNAseq data, leveraging as gold standard genes with in situ hybridization data from the Berkeley Drosophila Transcription Network Project reference atlas. The 34 participating teams used diverse algorithms for gene selection and location prediction, while being able to correctly localize rare subpopulations of cells. Selection of predictor genes was essential for this task and such genes showed a relatively high expression entropy, high spatial clustering and the presence of prominent developmental genes such as gap and pair-ruled genes and tissue defining markers.

systems biology↗

bioRxiv2019

H. pylori infection inhibits autophagy to aggravate DNA damage by p62-mediated Rad51 ubiquitination

Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric carcinogenesis. DNA damage response (DDR) and autophagy play key roles in tumorigenic transformation. However, it remains unclear how H. pylori infection modulate DNA damage and autophagy. Here we report that H. pylori infection promotes DNA damage via suppression of Rad51 expression through inhibition of autophagy and accumulation of p62 in gastric carcinogenesis. We find that H. pylori infection caused alteration of DDR pathway and autophagy in gastric cells and Mongolian gerbils in a CagA-dependent manner. Moreover, loss of autophagy led to promotion of DNA damage in H. pylori-infected cells. Furthermore, knockdown of autophagic substrate p62 upregulated Rad51 expression, and p62 promoted ubiquitination of Rad51 via the direct interaction of the UBA domain with Rad51. Finally, H. pylori infection was associated with elevated levels of p62 in gastric intestinal metaplasia and decreased levels of Rad51 in dysplasia compared to their H. pylori- counterparts. Our findings provide a novel mechanism into the linkage of H. pylori infection, autophagy, DNA damage and gastric tumorigenesis.

microbiology↗

bioRxiv2019

An efficient CRISPR-based strategy to insert small and large fragments of DNA using short homology arms

We previously reported a CRISPR-mediated knock-in strategy into introns of Drosophila genes, generating an attP-FRT-SA-T2A-GAL4-polyA-3XP3-EGFP-FRT-attP transgenic library for multiple uses (Lee et al., 2018b). The method relied on double stranded DNA (dsDNA) homology donors with [~]1 kb homology arms. Here, we describe three new simpler ways to edit genes in flies. We create single stranded DNA (ssDNA) donors using PCR and add 100 nt of homology on each side of an integration cassette, followed by enzymatic removal of one strand. Using this method, we generated GFP-tagged proteins that mark organelles in S2 cells. We then describe two dsDNA methods using cheap synthesized donors flanked by 100 nt homology arms and gRNA target sites cloned into a plasmid. Upon injection, donor DNA (1 to 5 kb) is released from the plasmid by Cas9. The cassette integrates efficiently and precisely in vivo. The approach is fast, cheap, and scalable.

genomics↗

bioRxiv2019

Improving Social Interactive Learning through Dual Brain Stimulation

Social interactive learning denotes the ability to acquire new information from a conspecific - a prerequisite for cultural evolution and survival. As inspired by recent neurophysiological research, here we tested whether social interactive learning can be augmented by exogenously synchronizing oscillatory brain activity across an instructor and a learner engaged in a naturalistic song-learning task. We used a dual brain stimulation protocol entailing the trans-cranial delivery of synchronized electric currents in two individuals simultaneously. When we stimulated inferior frontal brain regions, with 6 Hz alternating currents being in-phase between the instructor and the learner, the dyad exhibited spontaneous and synchronized body movement. Remarkably, this stimulation also led to enhanced learning performance. A mediation analysis further disclosed that interpersonal movement synchrony acted as a partial mediator of the effect of dual brain stimulation on learning performance, i.e. possibly facilitating the effect of dual brain stimulation on learning. Our results provide a causal demonstration that inter-brain synchrony is a sufficient condition to improve real-time information transfer between pairs of individuals.\n\nSignificanceThe study of social behavior, including but not limited to social learning, is undergoing a paradigm shift moving from single- to multi-person brain research. Yet, nearly all evidence in this area is purely correlational: inter-dependencies between brains signals are used to predict success in social behavior. For instance, inter-brain synchrony has been shown to be associated with successful communication, cooperation, and joint attention. Here we took a radically different approach. We stimulated two brains simultaneously, hence manipulating inter-brain synchrony, and measured the resulting effect upon behavior in the context of a social learning task. We report that frequency- and phase-specific dual brain stimulation can lead to the emergence of spontaneous synchronized body movement between an instructor and a learner. Remarkably, this can also augment learning performance.

neuroscience↗

bioRxiv2019

Germline RNA helicases couple RNA binding to P granule assembly at nuclear periphery

P granules are phase-separated liquid droplets that play important roles in the maintenance of the germ cell fate in C. elegans. The localization and formation of P granules are highly dynamic, but mechanisms that regulate such processes remain poorly understood. Here we show that germline RNA helicases (GLHs) control the formation and disassembly of germ granules through their binding and release of RNAs, respectively. In addition, the FGG repeats in the GLHs promote the formation of germ granules at the perinucleus. Proteomic analyses of a mutation that traps RNA-bound GLH-1 complex revealed transient interactions of GLH-1 with several Argonautes and RNA binding proteins. Finally, we found that defects in perinuclear P granule formation correlate with the fertility defects observed in various GLH mutants. Together, our results highlight the versatile roles of RNA helicases in controlling the formation of liquid droplets in space and time.

cell biology↗

bioRxiv2019

OmicsOne: Associate Omics Data with Phenotypes in One-Click

The rapid advancements of high-throughput \"omics\" technologies have brought huge amount of data to process during and after experiments. Multi-omic analysis facilitates a deeper interrogation of a dataset, and discovery of interesting genes, proteins, lipids, glycans, or metabolites, or pathways related to the corresponding phenotypes in a study. Many individual software tools have been developed to analyze and visualize the data. However, integrating multiple omics data analysis strategies and approaches in a single data processing pipeline is still a challenge task. OmicsOne is a software developed in R, Python and Jupyter Notebook that can achieve statistical analysis, machine learning, and data visualization on multi- omics data by taking the advantages of integrating the useful tools from individual software packages. OmicsOne can simplify \"omics\" data analysis, and delineate molecules, or pathways associated to interested phenotypes.

bioinformatics↗

bioRxiv2019

γ-Secretase controls the specification of astrocytes from oligodendrocyte precursor cells via Stat3

Oligodendrocytes (OLs) and astrocytes play critical roles in a variety of brain functions. OL precursor cells (OPCs) are known to give rise to OLs as well as astrocytes. However, little is known about the mechanism by which OPCs determine their specification choice for OLs versus astrocytes in the central nervous system (CNS). Here we show that genetic inhibition of {gamma}-secretase in OPCs reduces OL differentiation but enhances astrocyte specification. Mechanistic analysis reveals that inhibition of {gamma}-secretase results in decreased levels of Hes1, and that Hes1 down-regulates the expression of signal transducer and activator of transcription3 (Stat3) via binding to specific regions of its promoter. We demonstrate that conditional inactivation of Stat3 in OL lineages restores the number of astrocytes in {gamma}-secretase mutant mice. In summary, this study identifies a key mechanism which controls OPCs specification choice for OL versus astrocyte during postnatal development. This {gamma}-secretase-dependent machinery may be essential for the CNS to maintain the population balance between OLs and astrocytes.

neuroscience↗

bioRxiv2019

A systematic survey of PRMT interactomes reveals the key roles of arginine methylation in the global control of RNA splicing and translation

Thousands of proteins undergo arginine methylation, a widespread post-translational modification catalyzed by various protein arginine methyltransferases (PRMTs). However, a full picture of the catalytic network for each PRMT is lacking and the global understanding of their biological roles remains limited. Here we systematically identified interacting proteins for all human PRMTs and demonstrated that they are functionally important for mRNA splicing and translation. We showed that the interactomes of human PRMTs are significantly overlapped with the known methylarginine containing proteins, and different PRMTs are functionally complementary with a high degree of overlap in their substrates and high similarities between their putative methylation motifs. Importantly, arginine methylation is significantly enriched in RNA binding proteins involved in regulating RNA splicing and translation, and inhibition of PRMTs leads to global alteration of alternative splicing and suppression of translation. In particular, ribosomal proteins are pervasively modified with methylarginine, and mutations on their methylation sites suppress ribosome assembly, translation, and eventually cell growth. Collectively, our study provides a novel global view of different PRMT networks and uncovers critical functions of arginine methylation in the regulation of mRNA splicing and translation.

molecular biology↗

bioRxiv2019

Detecting differential alternative splicing events in scRNA-seq with or without UMIs

Analysis of alternative splicing in single-cell RNA sequencing (scRNA-seq) is challenging due to its inherent technical noise and generally low sequencing depth. We present SCATS (Single-Cell Analysis of Transcript Splicing) for differential alternative splicing (DAS) analysis for scRNA-seq data with or without unique molecular identifiers (UMIs). By modeling technical noise and grouping exons that originate from the same isoform(s), SCATS achieves high sensitivity to detect DAS events compared to Census, DEXSeq and MISO, and these events were confirmed by qRT-PCR experiment.

bioinformatics↗

bioRxiv2019

Enhance genome editing efficiency and specificity by a quick CRISPR/Cas9 system

CRISPR/Cas9 is a powerful genome editing tool that has been successfully applied to a variety of species, including zebrafish. However, targeting efficiencies vary greatly at different genomic loci, the underlying causes of which were still elusive. Here we report a quick CRISPR/Cas9 system, designated as qCas9, which exhibits accelerated turnover of Cas9 protein in zebrafish. Our data showed that qCas9 significantly improved targeting efficiency, including both knock-out and knock-in in F0 embryos, and yielded higher germline transmission rate in founder screen. Importantly, qCas9 showed little to no off-target editing in zebrafish and profoundly reduced off-target effect in HEK293T cell line. In summary, our findings demonstrate that qCas9 is a simple, economic and highly effective method to improve genome editing efficiency in zebrafish embryos and also holds great potential in reducing off-target effect in mammalian cell lines.

genetics↗

bioRxiv2019

Brain-to-brain coupling between instructors and learners discriminates between instructional approaches and predicts learning

The neural mechanisms that support naturalistic learning via effective pedagogical approaches remain elusive. Here we use functional near-infrared spectroscopy to measure brain activity from instructor-learner dyads simultaneously during dynamic conceptual learning. We report that brain-to-brain coupling is correlated with learning outcomes, and, crucially, appears to be driven by specific scaffolding behaviors on the part of the instructors (e.g., asking guiding questions or providing hints). Brain-to-brain coupling enhancement is absent when instructors use an explanation approach (e.g., providing definitions or clarifications). Finally, we find that machine-learning techniques are more successful when decoding instructional approaches (scaffolding vs. explanation) from brain-to-brain coupling data than when using a single-brain method. These findings suggest that brain-to-brain coupling as a pedagogically relevant measure tracks the naturalistic instructional process during instructor-learner interaction throughout constructive engagement, but not information clarification.

neuroscience↗

bioRxiv2019

A bibliometric analysis of Soil remediation Based on Massive research literature data During 1988-2018

Soil is an important part of the ecosystem with significant roles that help human population sustain. Research on prevention and remediation of soil pollution has been carried out when 1985. This study analyzed the 1988-2018 soil remediation dataset in the Web of Science database by bibliometric methods to illustrate the current research trends and hot topics of quantitative analysis and soil remediation in the world. To further identify the major soil contamination topics, we employed social network analysis. The results indicate that the field of soil remediation has entered a stage of rapid progress. The United States has a strong overall strength with the largest number of published articles and larger impact. China ranks second. We identified Journal of hazardous materials as the most influential journal and Chinese academy of sciences as the most influential institution. Academic cooperation showed an increasing trend at the author, institutional, and national levels with an average level of cooperation of 3.57, 1.66, and 1.16, respectively. However, the growth rate of cooperation at the national level is relatively low. In addition, the frequency and co-word analyses of keywords revealed the important research topics. \"heavy metals\", \"PAH\", \"bioremediation\", \"Phytoremediation\" and \"Electrokinetic remediation\" were identified as the hot topics. The findings of this study will help researchers understand the status of soil remediation as well as provide guidance for future research.

ecology↗

bioRxiv2019

Extreme tolerance of Paramecium to acute injury induced by γ rays

Due to the wide use of nuclear energy, nuclear radiation threat is increasing day by day. However, methods for protection against nuclear radiation are limited and not effective. Therefore, it is necessary to develop an effective method for protection and therapy against injury caused by radiation. According to the law of biological evolution, one of the most primitive eukaryotes, Paramecium, could be tolerant to ionizing radiations, in a way similar to or better than Ramazzottius varieornatus and Bdelloids rotifer. Therefore, in the present study, the anti-radiation effects of Paramecium were explored, which could be applicable to human beings. Paramecium was found to be tolerant to 60Co {gamma} rays, and its half lethal dose (LD50) was approximately 3000 Gy, which is 60 times more than that of human beings. The GSPATT00021409001 and GSPATT00016349001 genes were significantly up-regulated, which might play a role in DNA binding and nuclear transport, and thus, could function in DNA protection or repair. The biological function of the two genes and their effects in humans need to be explored in future studies.

cell biology↗

bioRxiv2019

BTLA and PD-1 employ distinct phosphatases to differentially repress T cell signaling

T cell-mediated destruction of tumors and virus-infected cells is restricted by co-inhibitory receptors such as programmed cell death protein 1 (PD-1). Monoclonal antibodies blocking PD-1 have produced impressive clinical activity against human cancers, but durable response is limited to a minority of patients. Previous results suggest that B and T lymphocyte attenuator (BTLA), a co-inhibitory receptor structurally related to PD-1, may contribute to the resistance to PD-1 targeted therapy and co-blockade of BTLA can enhance the efficacy of anti-PD-1 immunotherapy. However, the biochemical mechanism by which BTLA represses T cell activity and to what extent the mechanism differs from that of PD-1 is unknown. Here we examine differences in the ability of BTLA and PD-1 to recruit effector molecules and regulate T cell signaling. We show that PD-1 and BTLA recruit different tyrosine phosphatases to regulate either CD28 or T cell antigen receptor (TCR)-signaling cascades. Our data reveal unexpected disparities between two structurally related immune checkpoints and two phosphatase paralogs.

cell biology↗