Biology subjects

Cui, D.

Publications and source records attributed to Cui, D..

28 records · Page 2Linked to original sources

bioRxiv2021

Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines

IntroductoryThe evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic.

microbiology↗

bioRxiv2021

A chromosome-level reference genome of Ensete glaucum gives insight into diversity, chromosomal and repetitive sequence evolution in the Musaceae

BackgroundEnsete glaucum (2n = 2x = 18) is a giant herbaceous monocotyledonous plant in the small Musaceae family along with banana (Musa). A high-quality reference genome sequence of E. glaucum offers a vital genomic resource for functional and evolutionary studies of Ensete, the Musaceae, and more widely in the Zingiberales. FindingsUsing a combination of Illumina and Oxford Nanopore Technologies (ONT) sequencing, genome-wide chromosome conformation capture (Hi-C), and RNA survey sequence, we report a high-quality assembly of the 481.5Mb genome with 9 pseudochromosomes and 36,836 genes (BUSCO 94.7%). A total of 55% of the genome is composed of repetitive sequences with LTR-retroelements (37%) and DNA transposons (7%) predominant. The 5S and 45S rDNA were each present at one locus, and the 5S rDNA had an exceptionally long monomer length of c.1,056 bp, contrasting with the c. 450 bp monomer at multiple loci in Musa. A tandemly repeated c. 134 bp satellite, 1.1% of the genome (with no similar sequence in Musa), was present around all nine centromeres, with a LINE retroelement also found at Musa centromeres. The assembly, including centromeric positions, enabled us to characterize in detail the chromosomal rearrangements occurring between the x = 9 species and x = 11 species of Musa. Only one chromosome has the same gene content as M. acuminata (ma). Three ma chromosomes represent part of only one E. glaucum (eg) chromosome, while the remaining seven ma chromosomes are fusions of parts of two, three, or four eg chromosomes, demonstrating complex and multiple evolutionary rearrangements in the change between x = 9 and x = 11. ConclusionsThe advance towards a Musaceae pangenome including E. glaucum, tolerant of extreme environments, makes a complete set of gene alleles available for crop breeding and understanding environmental responses. The chromosome-scale genome assembly show how chromosome number evolves, and features of the rapid evolution of repetitive sequences.

plant biology↗

bioRxiv2021

Emergence of an adaptive epigenetic cell state in human bladder urothelial carcinoma evolution

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) facilitates therapy resistance and immune evasion to affect clinical prognosis directly. However, the molecular and cellular mechanism generating ITH in BLCA remains elusive. Here we show that a TM4SF1-positive cancer subpopulation (TPCS) drives ITH diversification in BLCA. By extensive profiling of the epigenome and transcriptome of BLCA from 79 donors across all stages, we elucidated the evolution trajectories of luminal and basal BLCA. TPCS emerges from the basal trajectory and shows extensive transcriptional plasticity with a distinct epigenomic landscape. Clinically, TPCS were enriched in advanced stage patients and associated with poor prognosis. Our results showed how cancer adapts to its environment by adopting a stem cell-like epigenomic landscape.

cancer biology↗

bioRxiv2021

SARS-CoV-2 susceptibility of cell lines and substrates commonly used in diagnosis and isolation of influenza and other viruses

Coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses is inevitable as the COVID-19 pandemic continues. This study aimed to evaluate cell lines commonly used in virus diagnosis and isolation for their susceptibility to SARS-CoV-2. While multiple kidney cell lines from monkeys were susceptible and permissive to SARS-CoV-2, many cell types derived from human, dog, mink, cat, mouse, or chicken were not. Analysis of MDCK cells, which are most commonly used for surveillance and study of influenza viruses, demonstrated that they were insusceptible to SARS-CoV-2 and that the cellular barrier to productive infection was due to low expression level of the angiotensin converting enzyme 2 (ACE2) receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by over-expression of canine ACE2 in trans. Moreover, SARS-CoV-2 cell tropism did not appear to be affected by a D614G mutation in the spike protein.

microbiology↗

bioRxiv2020

SARS-CoV-2 spike D614G variant confers enhanced replication and transmissibility

During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic1. However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro, it provides a real competitive advantage in vivo, particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

microbiology↗

bioRxiv2020

1RS.1BL molecular resolution provides novel contributions to wheat improvement

Wheat-rye 1RS.1BL translocation has a significant impact on wheat yield and hence food production globally. However, the genomic basis of its contributions to wheat improvement is undetermined. Here, we generated a high-quality assembly of 1RS.1BL translocation comprising 748,715,293 bp with 4,996 predicted protein-coding genes. We found the size of 1RS is larger than 1BS with the active centromere domains shifted to the 1RS side instead of the 1BL side in Aikang58 (AK58). The gene alignment showed excellent synteny with 1BS from wheat and genes from 1RS were expressed well in wheat especially for 1RS where expression was higher than that of 1BS for the grain-20DPA stage associated with greater grain weight and negative flour quality attributes. A formin-like-domain protein FH14 (TraesAK58CH1B01G010700) was important in regulating cell division. Two PPR genes were most likely the genes for the multi fertility restoration locus Rf multi. Our data not only provide the high-resolution structure and gene complement for the 1RS.1BL translocation, but also defined targets for enhancing grain yield, biotic and abiotic stress, and fertility restoration in wheat.

genomics↗

bioRxiv2020

Senile plaques in Alzheimer's disease are primarily induced by cerebral vesselleakage of red blood cells and other blood contents

The mechanism governing senile plaque generation in Alzheimers disease (AD) remains intensively debated. We analyzed AD brain tissues with histochemistry, immunohistochemistry and fluorescence imaging. We found little co-expression between neural markers and plaque A{beta} while abundant co-expression between blood or plasma markers such as HBA, HbA1C, Hemin, ApoE and plaque A{beta}. The cores of dense-core plaques were structured with vascular proteins and glial processes at the periphery and blood metabolites in the center. Senile plaques additionally co-localized with a characteristic Hoechst-staining-independent blue autofluorescence, likely also derived from red blood cells. A{beta} interacts with hemoglobin in an in vitro assay and also at single cell levels in red blood cells in vivo, showing as dots, stripes or diffusive patterns with its intensity correlated with coagulation, the elevation of calcium and blue autofluorescence. Interaction between A{beta} and ApoE in the blood stream forms vascular amyloid plaques that restrict red blood cell passage. The interaction of A{beta} and red blood cells associates with multiple blood and vascular defects besides CAA, including increased perivascular space, microaneurysm, intravascular hemolysis and vascular calcification. Senile plaque formation was intrinsically linked to vascular degeneration as shown by LRP1, ColIV and ACTA2 immunostaining. A{beta} staining also overlapped with Cathepsin D expression in intravascular hemolysis, CAA, microaneurysm and senile plaques in AD brain tissues. Microaneurysms with chronic hemolysis were identified as important sites of amyloid formation besides CAA and intravascular hemolysis. In summary, our data suggested that senile plaques arise from A{beta} and Cathepsin D-enriched amyloid mixtures out of intravascular hemolysis and Charcot-Bouchard aneurysm-related vascular degeneration. In addition, hemoglobin could be a primary physiological target of A{beta}.

cell biology↗

bioRxiv2019

PsyMuKB: A De Novo Variant Knowledge Base Integrating Transcriptional and Translational Information to Identify Isoform-specific Mutations in Developmental Disorders

De novo variants (DNVs) are one of the most significant contributors to severe early-onset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Currently, a plethora of DNVs have being identified through the use of next-generation sequencing and much effort has been made to understand their impact at the gene level; however, there has been little exploration of the impact at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues; therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate better usage and improve the isoform-level interpretation of variants, we developed the PsyMuKB (NeuroPsychiatric Mutation Knowledge Base), a knowledge base containing a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoform-specific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific de novo mutations for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.

bioinformatics↗

bioRxiv2019

Metabolic wastes are removed by excretosomes, nanotubes and exophers in mouse HT22 cells through an autophagic vesicle clustering mechanism

Neurodegenerative diseases are characterized by metabolic waste accumulations in neuronal cells. However, little is known about the mechanism of metabolic waste disposal. We showed that there is a constitutive waste excretion by nanotubes and structures called excretosomes in mouse neuronal HT22 cells under normal conditions and an exopher-type waste disposal under stressed conditions. Excretosomes and exophers are waste-enriched multivesicular bodies that are formed by autophagic vesicle clustering and fusions. Upon H2O2 treatment, metabolic waste marker intensified 1.4 to 3.4 fold. However, in dying H2O2-treated cells, glycolysis and stress response markers, alpha-Tubulin, Amyloid beta and alpha-Synuclein intensities reduced 30% to 80%. Amyloid beta, TAU and alpha-Synuclein associated with the autophagic vesicle clustering and fusion process and were excreted in large exophers by live oxidative-stressed cells before cell death with important implications for amyloid plaque, ghost tangle and Lewy body formation. H2O2 treatment also induced exophers containing nucleic acid materials and significantly increased the level of oxidative damage marker 8-OHdG. Oxidative stress-induced HT22 cell death could be due to the combinations of excretion failure, cytoskeleton disruption, defective glycolysis and DNA damage.

cell biology↗

bioRxiv2018

Optical and physical mapping with local finishing enables megabase-scale resolution of agronomically important regions in the wheat genome

BackgroundNumerous scaffold-level sequences for wheat are now being released and, in this context, we report on a strategy for improving the overall assembly to a level comparable to that of the human genome.\n\nResultsUsing chromosome 7A of wheat as a model, sequence-finished megabase scale sections of this chromosome were established by combining a new independent assembly based on a BAC-based physical map, BAC pool paired end sequencing, chromosome arm specific mate-pair sequencing and Bionano optical mapping with the IWGSC RefSeq v1.0 sequence and its underlying raw data. The combined assembly results in 18 super-scaffolds across the chromosome. The value of finished genome regions is demonstrated for two approximately 2.5 Mb regions associated with yield and the grain quality phenotype of fructan carbohydrate grain levels. In addition, the 50 Mb centromere region analysis incorporates cytological data highlighting the importance of non-sequence data in the assembly of this complex genome region.\n\nConclusionsSufficient genome sequence information is shown to be now available for the wheat community to produce sequence-finished releases of each chromosome of the reference genome. The high-level completion identified that an array of seven fructosyl transferase genes underpins grain quality and yield attributes are affected by five f-box-only-protein-ubiquitin ligase domain and four root-specific lipid transfer domain genes. The completed sequence also includes the centromere.

genomics↗