Biology subjects

Peng, Y.

Publications and source records attributed to Peng, Y..

At least 199 records · Page 11Linked to original sources

bioRxiv2021

Portrait of a genus: the genetic diversity of Zea

Maize is a globally valuable commodity and one of the most extensively studied genetic model organisms. However, we know surprisingly little about the extent and potential utility of the genetic variation found in the wild relatives of maize. Here, we characterize a high-density genomic variation map from ~700 genomes encompassing maize and all wild taxa of the genus Zea, identifying over 65 million single nucleotide polymorphisms (SNPs), 8 million Insertion/Deletion (InDel) polymorphisms, and over one thousand novel inversions. The variation map reveals evidence of selection within taxa displaying novel adaptations such as perenniality and regrowth. We focus in detail on evidence of convergent adaptation in highland teosinte and temperate maize. This study not only indicates the key role of hormone related pathways in highland adaptation and flowering time related pathways in high latitude adaptation, but also identifies significant overlap in the genes underlying adaptations to both environments. To show how this data can identify useful genetic variants, we generated and characterized novel mutant alleles for two flowering time candidate genes. This work provides the most extensive sampling to date of the genetic diversity inherent in the genus Zea, resolving questions on evolution and identifying adaptive variants for direct use in modern breeding.

evolutionary biology↗

bioRxiv2021

The impact of viral mutations on recognition by SARS-CoV-2 specific T-cells

We identify amino acid variants within dominant SARS-CoV-2 T-cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T-cells assessed by IFN-{gamma} and cytotoxic killing assays. These data demonstrate the potential for T-cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T-cell as well as humoral immunity.

immunology↗

bioRxiv2021

Twelve-month specific IgG response to SARS-CoV-2 receptor-binding domain among COVID-19 convalescent plasma donors in Wuhan

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.

immunology↗

bioRxiv2021

A meta-analysis of single visit pollination effectiveness

Many animals provide essential ecosystem services in the form of plant pollination. A rich literature documents considerable variation in the single visit pollination effectiveness of different plant visitors, but this literature has yet to be comprehensively synthesized. We conducted a hierarchical meta-analysis of 193 studies and extracted 1716 single visit effectiveness (SVE) comparisons for 252 plant species. We paired SVE data with visitation frequency data for 75 of these studies. Given the global dominance of honeybees in pollinator communities, we used these data to ask: 1) Do honeybees (Apis mellifera) and other floral visitors vary in their SVE?; 2) To what extent do plant and pollinator attributes predict the difference in SVE between honeybees and other visitors?; and 3) Is there a correlation between floral visitation frequency and SVE? We found that honeybees were significantly less effective than the most effective non-honeybee pollinator. Although not significantly different, honeybees also tended to be less effective than the mean community effectiveness. Honeybees were less effective as pollinators of crop plants and when compared to birds and other bees. Visitation frequency and pollination effectiveness were positively correlated, but this trend was largely driven by data from communities where honeybees were absent, suggesting that honeybees generally combine high visitation frequency and lower SVE. Our study demonstrates that non-honeybee floral visitors are highly effective pollinators of many crop and non-crop plants. While the high visitation frequency typically displayed by honeybees undoubtably makes them important pollinators, we show that honeybees are slightly less effective than the average pollinator and rarely the most effective pollinator of the plants they visit. As such, honeybees may be imperfect substitutes for the loss of wild pollinators and safeguarding global crop production will benefit from conservation of non-honeybee taxa. Open Research StatementAlthough we are fully committed to data transparency, we are also aware of different research teams working on related meta-analyses. As such, we prefer to wait until our paper is accepted to make data publicly available but are happy to share data upon request. Data will be permanently archived on Figshare following acceptance.

ecology↗

bioRxiv2021

Cooperative herbivory between two important pests of rice

Normally, when different species of herbivorous arthropods feed on the same plant this leads to fitness reducing competition. We found this to be uniquely different for two of Asias most destructive rice pests, the brown planthopper and the rice striped stem borer. Both insects directly and indirectly benefit from jointly attacking the same host plant. Double infestation improved plant quality, particularly for the stemborer because the planthopper fully suppresses caterpillar-induced production of proteinase inhibitors. It also drastically reduced the risk of egg parasitism, due to diminished parasitoid attraction. Females of both pests have adapted their oviposition behaviour accordingly. Their strong preference for plants infested by the other species even overrides their avoidance of plants already attacked by conspecifics. This uncovered cooperation between herbivores is telling of the exceptional adaptations resulting from the evolution of plant-insect interactions, and points out mechanistic vulnerabilities that can be targeted to control two major pests.

ecology↗

bioRxiv2021

Tumor protein D52 (TPD52) affects cancer cell metabolism by negatively regulating AMPK.

The AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, with deregulation leading to cancer and other diseases. When intracellular ATP levels decrease during energy stress, AMPK is phosphorylated and activated through AMP binding. However, how this pathway is dysregulated in cancer remains unclear. Here, we find that tumor protein D52 (TPD52), initially identified to be overexpressed in many human cancers, forms a stable complex with AMPK in cancer cells. TPD52 directly interacts with AMPK and inhibits AMPK kinase activity in vitro and in vivo. We generated TPD52 transgenic mice, and found that overexpression of TPD52 leads to AMPK inhibition and multiple metabolic defects in mice. Together, our results shed new light on AMPK regulation and on our understanding of the etiology of cancers with TPD52 overexpression.

cell biology↗

bioRxiv2021

Medulla glutamatergic neurons control wake-sleep transitions

Sleep is a ubiquitous behavior in animal species. Yet, brain circuits controlling sleep remain poorly understood. Previous studies have identified several brain structures that promote sleep, but whether these structures are involved in sleep initiation or sleep maintenance remains largely unknown. Here we identified a population of glutamatergic neurons in the medulla that project to the preoptic area (POA), a prominent sleep-promoting region. Chemogenetic silencing of POA-projecting medulla neurons disrupts the transitions from wakefulness to Non-Rapid Eye Movement (NREM) sleep, whereas chemogenetic activation of these neurons promotes NREM sleep. Moreover, we show that optogenetic activation of medulla glutamatergic neurons or their projections in the POA reliably initiates long-lasting NREM sleep in awake mice. Together, our findings uncover a novel excitatory brainstem-hypothalamic circuit that controls the wake-sleep transitions.

neuroscience↗

bioRxiv2021

Microbial tryptophan catabolism affects the vector competence of Anopheles

The influence of microbiota on mosquito physiology and vector competence is becoming increasingly clear but our understanding of interactions between microbiota and mosquitoes still remains incomplete. Here we show that gut microbiota of Anopheles stephensi, a competent malaria vector, participates mosquito tryptophan metabolism. Elimination of microbiota by antibiotics treatment leads to the accumulation of tryptophan (Trp) and its metabolites, kynurenine (Kyn), 3-hydroxykynurenine (3-HK) and xanthurenic acid (XA). Of these, 3-HK impairs the structure of peritrophic matrix (PM), thereby promoting Plasmodium berghei infection. Among the major gut microbiota in An. stephensi, Pseudomonas alcaligenes plays a role in catabolizing 3-HK as revealed by whole genome sequencing and LC-MS metabolic analysis. The genome of P. alcaligenes encodes kynureninase (KynU) that is responsible for the conversion of 3-HK to 3-Hydroxyanthranilic acid (3-HAA). Mutation of this gene abrogates the ability of P. alcaligenes to metabolize 3-HK, which in turn abolishes its role on PM protection. Colonization of An. stephensi with KynU mutated P. alcaligenes fails to protect mosquitoes against parasite infection as effectively as those with wild type bacterium. In summary, we identify an unexpected function of gut microbiota in controlling mosquito tryptophan metabolism with the major consequences on vector competence.

microbiology↗

bioRxiv2021

Physiological underpinning of default-mode network emergence in the human infant brain

Human infancy is characterized by most rapid cerebral blood flow (rCBF) increases across lifespan and emergence of a fundamental brain system default-mode network (DMN). However, how infant rCBF change spatiotemporally across the brain and how the rCBF dynamics support emergence of vital functional networks such as DMN remains unknown. Here, by acquiring cutting-edge multi-modal MRI including pseudo-continuous arterial-spin-labeled perfusion MRI and resting-state functional MRI of infants aged 0 to 24 months, we elucidated unprecedented 4D spatiotemporal infant rCBF framework and region-specific physiology-function coupling across infancy. We found faster rCBF increases in the DMN than other regions. We also found strongly coupled increases of rCBF and network strength specifically in the DMN, suggesting faster local blood flow increase to meet extra neuronal metabolic demands in the DMN maturation. These results offer insights into physiological mechanism of brain functional network emergence and have important implications in altered network maturation in brain disorders.

neuroscience↗

bioRxiv2021

A human antibody with blocking activity to RBD proteins of multiple SARS-CoV-2 variants including B.1.351 showed potent prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus macaques

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein for infection. After the virus sequence was published, we identified two potent antibodies against SARS-CoV-2 RBD from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a phase I clinical trial, showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.

microbiology↗

bioRxiv2020

High expression of JAM2 indicates better prognosis and immunotherapy response in breast cancer

In our study, multiple databases were used to explore the potential role and underlying mechanism of junctional adhesion molecule B (JAM2) in breast cancer (BRCA). The data of JAM2 was downloaded from The Cancer Cell Line Encyclopedia (CCLE), the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Receiver operating characteristic (ROC) curve analysis was performed to analyze the area under the curve (AUC) of JAM2 expression correlated with normal breast tissue and breast cancer tissue. Gene set enrichment analysis (GSEA) was used to identify the potential biological mechanisms of the JAM2. The expression of JAM2 mRNA were downregulated In most tumors, including BRCA, which may be due to the hypermethylated status. The AUCs, which were 0.929 and 0.887 by the logistic regression and random forest algorithms, indicated that JAM2 mRNA expression have good diagnostic value in BRCA. Univariate and multivariate analyses indicated JAM2 as an independent prognostic factor for the overall survival of BRCA patients in both the TCGA cohort (HR = 0.62, P = 0.034) and METABRIC cohort (HR = 0.77, P = 0.001). GSEA showed that multiple tumor pathways were suppressed in the JAM2 high expression group. The expression of JAM2 was most positively related to the epithelial-mesenchymal transition (EMT) score (r = 0.38; P <0.01) by the reverse-phase protein array (RPPA) analysis. Patients with high JAM2 expression may be more sensitive to immunotherapy. 18 chemotherapy drugs that patients in the JAM2 low expression group were more sensitive to were identified. Our results demonstrated the diagnostic and prognostic value of JAM2. Analysis of the molecular mechanisms indicates the potential role of JAM2 as a tumor suppressor, and high JAM2 expression may predict a better immunotherapy response in BRCA.

cancer biology↗

bioRxiv2020

Prokaryotic virus Host Predictor: a Gaussian model for host prediction of prokaryotic viruses in metagenomics

BackgroundViruses are ubiquitous biological entities, estimated to be the largest reservoirs of unexplored genetic diversity on Earth. Full functional characterization and annotation of newly-discovered viruses requires tools to enable taxonomic assignment, the range of hosts, and biological properties of the virus. Here we focus on prokaryotic viruses, which include phages and archaeal viruses, and for which identifying the viral host is an essential step in characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus, which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts, which needs improvements at both accuracy and usability. Here we develop a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. ResultsWe present here Prokaryotic virus Host Predictor (PHP), a software tool using a Gaussian model, to predict hosts for prokaryotic viruses using the differences of Ae-mer frequencies between viral and host genomic sequences as features. PHP gave a host prediction accuracy of 34% (genus level) on the VirHostMatcher benchmark dataset and a host prediction accuracy of 35% (genus level) on a new dataset containing 671 viruses and 60,105 prokaryotic genomes. The prediction accuracy exceeded that of two alignment-free methods (VirHostMatcher and WIsH, 28%-34%, genus level). PHP also outperformed these two alignment-free methods much (24%-38%vs 18%-20%, genus level) when predicting hosts for prokaryotic viruses which cannot be predicted by the BLAST-based or the CRISPR-spacer-based methods alone. Requiring a minimal score for making predictions (thresholding) and taking the consensus of the top 30 predictions further improved the host prediction accuracy of PHP. ConclusionsThe Prokaryotic virus Host Predictor software tool provides an intuitive and user-friendly API for the Gaussian model described herein. This work will facilitate the rapid identification of hosts for newly-identified prokaryotic viruses in metagenomic studies. Author SummaryProkaryotic viruses which include phages and archaeal viruses play an important role in balancing the global ecosystem by regulating the composition of bacteria and archaea in water and soil. Identifying the viral host is essential for characterizing the virus, as the virus relies on the host for survival. Currently, the method for determining the viral host is either to culture the virus which is low-throughput, time-consuming, and expensive, or to computationally predict the viral hosts which needs improvements at both accuracy and usability. This study developed a Gaussian model to predict hosts for prokaryotic viruses with better performances than previous computational methods. It will contribute to the rapid identification of hosts for prokaryotic viruses in metagenomic studies, and will extend our knowledge of virus-host interactions.

bioinformatics↗

bioRxiv2020

Binding of regulatory proteins to nucleosomes is modulated by dynamic histone tails

Despite histone tails critical roles in epigenetic regulation, little is known about mechanisms of how histone tails modulate the nucleosomal DNA solvent accessibility and recognition of nucleosomes by other macromolecules. Here we generate extensive atomic level conformational ensembles of histone tails in the context of the full human nucleosome, totaling 26 microseconds of molecular dynamics simulations. We explore the histone tail binding with the nucleosomal and linker DNA and observe rapid conformational transitions between bound and unbound states allowing us to estimate kinetic and thermodynamic properties of the histone tail-DNA interactions. Different histone types exhibit distinct, although conformationally heterogeneous, binding modes and each histone type occludes specific DNA regions from the solvent. Using a comprehensive set of experimental data on nucleosome structural complexes, we find that majority of the studied nucleosome-binding proteins and histone tails target mutually exclusive regions on nucleosomal or linker DNA around the super-helical locations {+/-}1, {+/-}2, and {+/-}7. This finding is explained within the generalized competitive binding and tail displacement models of partners recruitment to nucleosomes. Finally, we demonstrate the crosstalk between different histone post-translational modifications, where charge-altering modifications and mutations typically suppress tail-DNA interactions and enhance histone tail dynamics.

biophysics↗

bioRxiv2020

Genomic surveillance and improved molecular typing of Bordetella pertussis using wgMLST

Multi-Locus Sequence Typing (MLST) provides allele-based characterization of bacterial pathogens in a standardized framework. However, current MLST schemes for Bordetella pertussis, the causative agent of whooping cough, seldom reveal diversity among the small number of gene targets and thereby fail to delineate population structure. To improve discriminatory power of allele-based molecular typing of B. pertussis, we have developed a whole-genome MLST (wgMLST) scheme from 214 reference-quality genome assemblies. Iterative refinement and allele curation resulted in a scheme of 3,506 coding sequences and covering 81.4% of the B. pertussis genome. This wgMLST scheme was further evaluated with data from a convenience sample of 2,389 B. pertussis isolates sequenced on Illumina instruments, including isolates from known outbreaks and epidemics previously characterized by existing molecular assays, as well as replicates collected from individual patients. wgMLST demonstrated concordance with whole-genome single nucleotide polymorphisms (SNP) profiles, accurately resolved outbreak and sporadic cases in a retrospective comparison, and clustered replicate isolates collected from individual patients during diagnostic confirmation. Additionally, a re-analysis of isolates from two statewide epidemics using wgMLST reconstructed the population structures of circulating strains with increased resolution, revealing new clusters of related cases. Comparison with an existing core-genome (cgMLST) scheme highlights the genomic stability of this bacterium and forms the initial foundation for necessary standardization. These results demonstrate the utility of wgMLST for improving B. pertussis characterization and genomic surveillance during the current pertussis disease resurgence.

microbiology↗

bioRxiv2020

Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

Radial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted "intermediate" precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.

developmental biology↗

bioRxiv2020

Novel inhibitors of E. coli lipoprotein diacylglyceryl transferase are insensitive to resistance caused by lpp deletion

Lipoprotein diacylglyceryl transferase (Lgt) catalyzes the first step in the biogenesis of Gram-negative bacterial lipoproteins which play crucial roles in bacterial growth and pathogenesis. We demonstrate that Lgt depletion in a clinical uropathogenic Escherichia coli strain leads to permeabilization of the outer membrane and increased sensitivity to serum killing and antibiotics. Importantly, we identify the first ever described Lgt inhibitors that potently inhibit Lgt biochemical activity in vitro and are bactericidal against wild-type Acinetobacter baumannii and E. coli strains. Unlike inhibition of other steps in lipoprotein biosynthesis, deletion of the major outer membrane lipoprotein, lpp, is not sufficient to rescue growth after Lgt depletion or provide resistance to Lgt inhibitors. Our data validate Lgt as a novel druggable antibacterial target and suggest that inhibition of Lgt may not be sensitive to one of the most common resistance mechanisms that invalidate inhibitors of downstream steps of bacterial lipoprotein biosynthesis and transport.

microbiology↗

bioRxiv2020

New evidence concerning the genome designations of the AC(DC) tetraploid Avena species

The tetraploid Avena species in the section Pachycarpa Baum, including A. insularis, A. maroccana, and A. murphyi, are thought to be involved in the evolution of hexaploid oats; however, their genome designations are still being debated. Repetitive DNA sequences play an important role in genome structuring and evolution, so understanding the chromosomal organization and distribution of these sequences in Avena species could provide valuable information concerning genome evolution in this genus. In this study, the chromosomal organizations and distributions of six repetitive DNA sequences (including three SSR motifs (TTC, AAC, CAG), one 5S rRNA gene fragment, and two oat A and C genome specific repeats) were investigated using non-denaturing fluorescence in situ hybridization (ND-FISH) in the three tetraploid species mentioned above and in two hexaploid oat species. Preferential distribution of the SSRs in centromeric regions was seen in the A and D genomes, whereas few signals were detected in the C genomes. Some intergenomic translocations were observed in the tetraploids; such translocations were also detected between the C and D genomes in the hexaploids. These results provide robust evidence for the presence of the D genome in all three tetraploids, strongly suggesting that the genomic constitution of these species is DC and not AC, as had been thought previously.

genetics↗

bioRxiv2020

Keratin5-BMP4 mechanosignaling regulates reciprocal acetylation and methylation at H3K9 to define blastema cell remodeling during zebrafish heart regeneration

Heart regeneration after myocardial infarction remains challenging due to scar and ischemia-reperfusion injury. Here, we show that zebrafish blastema regeneration can effectively resalvage the wound myocardium and blood clot through cytoplasmic exocytosis and nuclear reorganization. The cell remodeling process are also visualized by spatiotemporal expression of three core blastema genes: alpha-SMA- which marks for fibrogenesis, Flk1for angiogenesis/hematopoiesis, Pax3a for remusculogensis, and by characteristic chromatin depositions of H3K9Ac/H3K9Me3. Genome-wide enhancer identification links the depositions of the two histone marks to the chromatin state and these three core blastema cell phenotypes. When the blastema subcellular fractions are introduced into the cultured zebrafish embryonic fibroblasts the altered transcription profile is comparable to the blastema transcription in terms of extracellular matrix structural constituent, vasculature development/angiogenesis, and cardiac muscle regeneration. From the subcellular fractions we identify 15 extracellular components and intermediate filaments, and show that introduction of human Krt5 and noggin peptides conversely regulate PAC2 cells F-actin reorganization, chromatin depositions of H3K9Ac/ H3K9Me3 and phosphorylation of Smad, which are accompanied by characteristic transcriptions of bmp, bmp4, three core blastema genes as well as specific histone acetylation/methylation-related genes. Collectively, this study establishes a new Krt5-BMP4 mechanosignaling cascade that links extracellular molecules to chromatin modifications and regulates blastema cell remodeling, thus providing mechanistic insights into the mesoderm-derived blastema regeneration and underlining a therapy strategy for myocardial infarction.

cell biology↗