Biology subjects

Cui, Y.

Publications and source records attributed to Cui, Y..

At least 163 records · Page 9Linked to original sources

bioRxiv2022

HSP90.6 is involved in grain filling via carbon and nitrogen metabolism in maize.

Carbon and nitrogen are the two most abundant nutrients in all living things, and their metabolism maintains normal plant growth. However, the molecular mechanism underlying carbon and nitrogen metabolism remains largely unknown. Here, we found that HSP90.6 is involved in the metabolism of carbon and nitrogen. We performed gene cloning and functional characterization of a maize EMS mutant ehsp90.6, whose kernels were small. HSP90.6 encodes heat shock protein 90.6, which has a single-amino acid mutation within its HATPase_c domain. Transcriptome profiling showed that the expression of amino acid biosynthesis- and carbon metabolism-related genes was significantly downregulated in hsp90.6. HSP90.6 is involved in the 26S proteasome degradation pathway, which affects nitrogen recycling to regulate amino acid synthesis; this occurs by interactions between HSP90.6 and the 26S proteasome subunits RPN6 and PBD2 (PRC2). The loss of HSP90.6 significantly reduced the activity of the 26S proteasome, resulting in the accumulation of ubiquitinated proteins and defects in nitrogen recycling. Moreover, HSP90.6 interacted with the 14-3-3 protein GF14-6 to participate in carbon metabolism. Together, these findings revealed that HSP90.6 regulates nutrient metabolism in maize seeds by affecting 26S proteasome-mediated nitrogen recycling and GF14-6-mediated carbon metabolism. One sentence summaryHSP90.6 is involved in nutrient metabolism via 26S proteasome-mediated protein degradation to promote nitrogen recycling and GF14-6 protein-mediated carbon metabolism. The author responsible for the distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (https://academic.oup.com/plcell/pages/General-Instructions) is Weibin Song (songwb@cau.edu.cn). HighlightsO_LIHATPase_c is necessary for HSP90.6 to regulate maize kernel development. C_LIO_LIHSP90.6 is involved in nitrogen recycling via the 26S proteasome degradation pathway. C_LIO_LIHSP90.6 interacts with the 14-3-3 protein GF14-6 to affect carbon metabolism. C_LI IN A NUTSHELLO_ST_ABSBackgroundC_ST_ABSSeeds are the main harvested organs of maize. Understanding the regulatory mechanism of grain filling is helpful to cultivate high-quality and high-yield maize. In the past few years, the regulatory network of grain filling has been explored through multiple means, including transcriptomic, proteomic and functional genomic techniques. Many genes that control grain filling through different mechanisms have been cloned, such as CTLP1 (Choline Transporter-like Protein 1), OS1 (Opaque Endosperm and Small Germ 1), and MN6 (Miniature Seed6). To identify new genes involved in maize grain filling, ethyl methanesulfonate (EMS) was used to induce mutations, and the ehsp90.6 mutant, which exhibited abnormal kernel development, was isolated by bulked segregant analysis RNA sequencing (BSR). QuestionWhy does the single-amino acid mutation of HSP90.6 affect grain size, and how does the loss of HSP90.6 affect grain filling? FindingsA single-amino acid mutant (ehsp90.6) and knockout mutant (hsp90.6) were obtained. We found that HSP90-6 was involved in the regulation of maize grain filling. A single-single amino acid mutation in the HATPase_c domain reduced the ATPase activity of HSP90.6, resulting in smaller grains. The functional loss of HSP90.6 resulted in the expression of amino acid biosynthesis- and carbon metabolism-related genes being significantly downregulated in hsp90.6. We indicated that HSP90.6 is involved in the 26S proteasome degradation pathway, which affects nitrogen recycling to regulate amino acid synthesis by interacting with the 26S proteasome subunits RPN6 and PBD2 (PRC2). Moreover, HSP90.6 was found to interact with the 14-3-3 protein GF14-6 to participate in carbon metabolism. Next stepsTo further verify that the interaction between HSP90.6 and 26S proteasome subunits and GF14-6 affects grain filling, knockout validation of RPN6, PBD2 (PRC2) and GF14-6 will be performed. In addition, since GF14-6 interacts with the phosphorylated proteins, we will determine the phosphorylation site of HSP90.6. Due to the important role of HSP90 family proteins in plant development, there are other regulatory pathways that need to be explored.

plant biology↗

bioRxiv2022

Extensive diversity of RNA viruses in ticks revealed by metagenomics in northeastern China

Recently, several emerging tick-borne viruses have been identified to be associated with human diseases in northeastern China. Here, we used metagenomics to investigate the virome diversity in Haemaphysalis japonica, H. conicinna, Dermacentor silvarum, and Ixodes persulcatus ticks in northeastern China. A total of 22 RNA viruses were identified and belonged to more eight viral families, including four each in Nairoviridae and Phenuiviridae, three each in Flaviviridae, Rhabdoviridae, and Solemoviridae, two in Chuviridae, and one each in Partitiviridae, Tombusviridae, and unclassified. Of them, eight viruses were novel species, belonging to Nairoviridae (Jian nairovirus and Yichun nairovirus), Phenuiviridae (Mudanjiang phlebovirus), Rhabdoviridae (Tahe rhabdovirus 1-3), Chuviridae (Yichun mivirus), and Tombusviridae (Yichun tombus-like virus), and five members were established human pathogens, including Alongshan virus, tick-borne encephalitis virus, Songling virus, Beiji nairovirus, and Nuomin virus. I. persulcatus ticks had significant higher viral species than those in H. japonica, H. concinna, and D. silvarum ticks. Significant differences in tick viromes were observed among Daxingan, Xiaoxingan and Changbai mountains. These findings showed an extensive diversity of RNA viruses in ticks in northeastern China, revealed potential public health threats from the emerging tick-borne viruses. Further studies are needed to explain the natural circulation and pathogenicity of these viruses.

microbiology↗

bioRxiv2022

Antibody Resistance of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2 and BA.3 Sub-lineages

The SARS-CoV-2 Omicron variant has been partitioned into four sub-lineages designated BA.1, BA.1.1, BA.2 and BA.3, with BA.2 becoming dominant worldwide recently by outcompeting BA.1 and BA.1.1. We and others have reported the striking antibody evasion of BA.1 and BA.2, but side-by-side comparison of susceptibility of all the major Omicron sub-lineages to vaccine-elicited or monoclonal antibody (mAb)-mediated neutralization are urgently needed. Using VSV-based pseudovirus, we found that sera from individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV) showed very weak to no neutralization activity, while a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) markedly improved the neutralization titers against all Omicron variants. The comparison between sub-lineages indicated that BA.1.1, BA.2 and BA.3 had comparable or even greater antibody resistance than BA.1. We further evaluated the neutralization profile of a panel of 20 mAbs, including 10 already authorized or approved, against these Omicron sub-lineages as well as viruses with different Omicron spike single or combined mutations. Most mAbs lost their neutralizing activity completely or substantially, while some demonstrated distinct neutralization patterns among Omicron sub-lineages, reflecting their antigenic difference. Taken together, our results suggest all four Omicron sub-lineages threaten the efficacies of current vaccines and antibody therapeutics, highlighting the importance of vaccine boosters to combat the emerging SARS-CoV-2 variants.

microbiology↗

bioRxiv2022

Role of MULE activities in the positive selection of sweet orange cultivars

Sweet orange (SWO) has one of the largest numbers of cultivar groups in Citrus with diverse horticultural traits just through asexual breeding. However, the molecular mechanism driving its fast selection and diversification is unclear. In this study, we completely surveyed the transposon activities in SWO genomes and unraveled six transposon families with up to 8,974.2-fold activity increase in modern SWO cultivars. Based on the transposon insertion phylogenetic tree, we inferred that modern SWOs date back to a common ancestor [~]500 years ago and reconstructed three major spread events in SWO cultivation history. Activation, acceleration, and silencing of the six families have recurred in distinct lineages. Their insertions are presented as tag mutations for all SWO cultivar groups and can distinguish over 99% of all analyzed SWO accessions. The insertions are enriched in impacting plant development and hormone signaling. This study demonstrated the importance of transposon activities in asexual breeding.

genetics↗

bioRxiv2022

Structural connectivity gradient associated with a dichotomy reveals the topographic organization of the macaque insular cortex

Histology studies revealed that the macaque insular cortex was characterized by the gradual organizations containing agranular, dysgranular and granular insula. However, no consensus has been reached on the elaborate subdivisions of macaque insula. Until now, no neuroimaging study to our knowledge combining connectivity-based gradients and parcellation has been performed to investigate the topographic organization of the macaque insular cortex. In this study, we used high-resolution ex vivo diffusion-weighted imaging data to explore the macaque insular cortexs global gradient organization and subdivisions. We found a rostrocaudal organization of the dominant gradient in the macaque insula using a diffusion map embedding. Meanwhile, extracting the 25% top and bottom components from the dominant and second gradient, which explained variance over 60% in total within ten gradients, the connectivity-based parcellation method was performed to subdivide each component into two subregions confirmed by the cross-validation analysis. Furthermore, permutations tests identified that two subregions from each component showed significant differences between their connectivity fingerprints. Finally, we found that the dominant and second gradients were significantly correlated with the T1w/T2w and cortical thickness maps in the macaque insula. Taken together, the global gradients combining the subdivisions examined the topographic organization of the macaque insular cortex based on the structural connectivity, which may contribute to a better understanding of the intricate insular cortex anatomy.

neuroscience↗

bioRxiv2022

Drivers of nematode diversity in forest soils across climatic zones

Nematodes are the most abundant multi-cellular animals in soil, influencing key processes and functions in terrestrial ecosystems. Yet, little is known about the drivers of nematode abundance and diversity in forest soils across climatic zones. This is despite forests cover approximately 30% of the earths land surface, provide many crucial ecosystem services but strongly vary in hydrothermal conditions and associated ecosystem properties across climatic zones. Here, we collected nematode samples from 13 forests across a latitudinal gradient. We divided this gradient in temperate, warm-temperate, and tropical climatic zones. Using boosted regression trees, we showed that across the gradient, nematode abundance and diversity were mainly influenced by soil organic carbon. However, within climatic zones, other factors were more important in driving nematode alpha-diversity, nematode biomass and the abundance of different trophic groups: mean annual temperature and total soil phosphorus in temperate zones, soil pH in warm-temperate zones, and mean annual precipitation in tropical zones. Additionally, nematode beta-diversity was higher in temperate than in warm-temperate and tropical zones, and we did not find significant differences among climatic zones in nematode gamma diversity. Together, our findings indicate a latitudinal shift in the main climatic variables controlling soil nematode communities and demonstrate that the drivers of soil nematode diversity in forested ecosystems are affected by the spatial scale and climatic conditions considered. This implies that high resolution studies are needed to accurately predict how soil functions respond if climate conditions move beyond the coping range of soil organisms. Our results also emphasize the importance of studying the area-diversity relationship of soil organisms under different climatic conditions.

ecology↗

bioRxiv2022

A Neuropsin-based Optogenetic Tool for Precise Control of Gq signaling

Gq-coupled receptors regulate numerous physiological processes by activating enzymes and inducing intracellular Ca2+ signals. There is a strong need for an optogenetic tool that enables powerful experimental control over Gq signaling. Here, we present chicken opsin 5 (cOpn5) as the long sought-after, single-component optogenetic tool that mediates ultra-sensitive optical control of intracellular Gq signaling with high temporal and spatial resolution. Expressing cOpn5 in mammalian cells enables blue light-triggered, Gq-dependent Ca2+ release from intracellular stores and protein kinase C activation. Strong Ca2+ transients were evoked by brief light pulses of merely 10 ms duration and at 3 orders lower light intensity of that for common optogenetic tools. Photostimulation of cOpn5-expressing cells at the subcellular and single-cell levels generated intracellular and intercellular Ca2+ wave propagation, respectively, thus demonstrating the high spatial precision of cOpn5 optogenetics. The cOpn5-mediated optogenetics could also be applied to activate neurons and control animal behavior in a circuit-dependent manner. We further revealed that optogenetic activation of cOpn5-expressing astrocytes induced massive ATP release and modulation neuronal activation in the brain of awake, behaving mice. cOpn5 optogenetics may find broad applications in studying the mechanisms and functional relevance of Gq signaling in both non-excitable cells and excitable cells in all major organ systems.

neuroscience↗

bioRxiv2022

Microbial dysbiosis and metabolic disorders promote rheumatoid arthritis progression across successive stages

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease that typically progresses through four stages, from mild stiffness to severe disability. The critical involvement of gut microbial dysbiosis in promoting RA has been intriguing. The aim of this study was to investigate stage-specific roles of microbial dysbiosis and metabolic disorders in pathogenesis across successive stages of RA. MethodsIn this multi-omics cohort study, fecal metagenomic, plasma metabolomic data were collected from 76 patients grouped into four RA stages, 19 patients with osteoarthritis, and 27 healthy individuals in China. A non-redundant gene catalogue was constructed, functionally annotated, and clustered into metagenomic species (MGS). Leave-one-out analysis was performed to determine the MGS that most drove the microbial dysfunctions with RA across stages. Random forest algorithm was performed to investigate diagnostic potential of microbial or metabolic features for each stage. Additionally, to verify the bacterial invasion of the joint synovial fluid, we conducted 16S rRNA gene sequencing, bacterial isolation, and scanning electron microscopy on joint synovial fluid from another cohort of 271 RA patients grouped into four RA stages. FindingsWe found that microbial dysbiosis and metabolic disorders had stage-specific effects on RA progression. For instance, arginine succinyltransferase pathway was elevated mainly in the second and third stages of RA (p=1{middle dot}4x10-3), which was driven by Escherichia coli, and it was correlated with the increase of the rheumatoid factor (p=1{middle dot}35x10-3). Considerable elevation of methoxyacetic acid (p=1{middle dot}28x10-8) and cysteine-S-sulfate (p=4{middle dot}66x10-12) might inhibit osteoblasts in the second stage and enhance osteoclasts in the third stage, respectively. Moreover, fecal microbes Eggerthella lenta and Bifidobacterium longum that were exclusively elevated in the fourth stage, were also detected in the joint synovial fluid. InterpretationOur findings elucidate for the first time the stage-specific roles of microbial dysbiosis and metabolic disorders across successive stages of RA, which open up new avenues for RA prognosis and therapy. We demonstrate the buildup of these effects might induce microbial invasion of the joint synovial fluid in the fourth stage of RA.

microbiology↗

bioRxiv2022

Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex

The prefrontal cortex (PFC) is a highly variable, evolutionarily expanded brain region that is engaged in multiple cognitive processes. The subregions of the PFC mature relatively late compared with other brain regions, and the maturation times vary between these subregions. Among these, the dorsomedial and dorsolateral prefrontal cortex (dmPFC and dlPFC) share a parallel topographic pattern of functional connectivity, while participating in different types of complex behaviors. However, the developmental trajectories of the two areas remain obscure. In this study, we uncovered differences in the developmental trends of the dmPFC and dlPFC. These differences were mainly caused by structural and functional changes in the medial area of the superior frontal gyrus (SFG). The developmentally different arealization patterns were verified using multiple parcellation approaches with multimodal data, including structural magnetic resonance imaging (sMRI), diffusion MRI (dMRI), resting state functional MRI (rfMRI), and a publicly available transcriptomic dataset. Human brain gene expression data was also used to perform downstream analyses, which could inform us about the potential biological mechanisms underlying the developmentally different arealizations. Furthermore, behavioral analyses hinted at the effects of regionalization on ontogeny. In brief, this study revealed a tendency toward a medial-lateral prefrontal division and can provide a fuller understanding of the potential underlying genetic underpinnings as well as of the potential effects on developmental behavior.

neuroscience↗

bioRxiv2022

Clinical Time-to-Event Prediction Enhanced by Incorporating Compatible Related Outcomes

Accurate time-to-event (TTE) prediction of clinical outcomes from personal biomedical data is essential for precision medicine. It has become increasingly common that clinical datasets contain information for multiple related patient outcomes from comorbid diseases or multifaceted endpoints of a single disease. Various TTE models have been developed to handle competing risks that are related to mutually exclusive events. However, clinical outcomes are often non-competing and can occur at the same time or sequentially. Here we develop TTE prediction models with the capacity of incorporating data of compatible related clinical outcomes. We test our method on real and synthetic data and find that the incorporation of related auxiliary clinical outcomes can: 1) significantly improve the TTE prediction performance of convention Cox model while maintaining its interpretability; 2) further improve the performance of the state-of-the-art deep learning based models. While the auxiliary outcomes are utilized for model training, the model deployment is not limited by the availability of the auxiliary outcome data because the auxiliary outcome information is not required for the prediction of the primary outcome once the model is trained.

bioinformatics↗

bioRxiv2022

Elevated FAM84B promotes cell proliferation via interacting with NPM1 in esophageal squamous cell carcinoma

Family with sequence similarity 84, member B (FAM84B) is a significant copy number amplification gene in the 8q24.21 locus identified by our previous WGS study in esophageal squamous cell carcinoma (ESCC). However, its clinical relevance and potential mechanisms have been elusive. Here, we performed the association analyses between FAM84BAmp and clinicopathological features using our dataset with 507 ESCC samples. The results indicated that, compared with the FAM84Bnon-Amp patients, the FAM84BAmp patients showed a more aggressive and a worse prognosis. Significant correlation was discovered between the expression level of FAM84B and FAM84BAmp in ESCC cohort. Furthermore, we found that the forced expression change of FAM84B can influence ESCC cell proliferation and cell cycle status, which is probably mediated by NPM1. A direct interaction between FAM84B and the C-terminal (189-294aa) of NPM1 was identified, which increased the NPM1 nuclear expression. Over-expression of NPM1 could inhibit the CDKN2A protein expression, which might affect the ESCC cell cycle. Our results indicate FAM84B CNA may be a potential diagnostic and therapeutic biomarker in ESCC, meanwhile, reveal a novel mechanism of FAM84B that it promotes tumorigenesis via interacting with NPM1 and suppressing CDKN2A.

cancer biology↗

bioRxiv2021

Homologous or Heterologous Booster of Inactivated Vaccine Reduces SARS-CoV-2 Omicron Variant Escape from Neutralizing Antibodies

The massive and rapid transmission of SARS-CoV-2 has led to the emergence of several viral variants of concern (VOCs), with the most recent one, B.1.1.529 (Omicron), which accumulated a large number of spike mutations, raising the specter that this newly identified variant may escape from the currently available vaccines and therapeutic antibodies. Using VSV-based pseudovirus, we found that Omicron variant is markedly resistant to neutralization of sera form convalescents or individuals vaccinated by two doses of inactivated whole-virion vaccines (BBIBP-CorV). However, a homologous inactivated vaccine booster or a heterologous booster with protein subunit vaccine (ZF2001) significantly increased neutralization titers to both WT and Omicron variant. Moreover, at day 14 post the third dose, neutralizing antibody titer reduction for Omicron was less than that for convalescents or individuals who had only two doses of the vaccine, indicating that a homologous or heterologous booster can reduce the Omicron escape from neutralizing. In addition, we tested a panel of 17 SARS-CoV-2 monoclonal antibodies (mAbs). Omicron resists 7 of 8 authorized/approved mAbs, as well as most of the other mAbs targeting distinct epitopes on RBD and NTD. Taken together, our results suggest the urgency to push forward the booster vaccination to combat the emerging SARS-CoV-2 variants.

microbiology↗

bioRxiv2021

On-tissue spatial proteomics integrating MALDI-MS imaging with shotgun proteomics reveals soy consumption-induced biomarkers in a fragile X syndrome mouse model

Soy-based diets are associated with increased seizures and autism. Thus, there is an acute need for unbiased protein biomarker identification in Fragile X syndrome (FXS) in response to soy consumption. Herein, we present a spatial proteomics approach integrating mass spectrometry imaging (MSI) with label-free proteomics in a mouse model of FXS to map the spatial distribution and quantify the levels of proteins in the hippocampus and hypothalamus brain regions. In total, 1,004 unique peptides were spatially resolved, demonstrating the diverse array of peptidomes present in the tissue slices and the broad coverage of the strategy. A group of proteins that are known to be involved in the GABAergic system, synaptic transmission, and co-expression network analysis indicated that protein in soy group was significantly associated with metabolism and synapse modules in the Fmr1KO brain. Ultimately, this spatial proteomics work laid the ground for identifying novel therapeutic targets and biomarkers for FXS.

biochemistry↗

bioRxiv2021

Sleep Need, the Key Regulator of Sleep Homeostasis, Is Indicated and Controlled by Phosphorylation of Threonine 221 in Salt Inducible Kinase 3

Sleep need drives sleep and plays a key role in homeostatic regulation of sleep. So far sleep need can only be inferred by animal behaviors and indicated by electroencephalography (EEG). Here we report that threonine 221 (T221) of the salt inducible kinase 3 (SIK3) was important for the catalytic activity and stability of SIK3. T221 phosphorylation in the mouse brain indicates sleep need: more sleep resulting in less phosphorylation and less sleep more phosphorylation during daily sleep/wake cycle and after sleep deprivation (SD). Sleep need was reduced in SIK3 loss of function (LOF) mutants and by T221 mutation to alanine (T221A). Sleep rebound after SD was also decreased in SIK3 LOF and T221A mutant mice. Other kinases such as SIK1 and SIK2 or other sites in SIK3 do not fulfil criteria to be both an indicator and a controller of sleep need. Our results reveal SIK3 T221 phosphorylation as the first and only chemical modification which indicates and controls sleep need.

neuroscience↗

bioRxiv2021

Addition of a carboxy terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice

Gonadotropin-releasing hormone (GnRH) is the primary neuropeptide controlling reproduction in vertebrates. GnRH stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis via a G protein-coupled receptor, GnRHR, in the pituitary gland. In mammals, GnRHR lacks a C-terminal cytosolic tail (Ctail) and does not exhibit homologous desensitization. This might be an evolutionary adaptation that enables LH surge generation and ovulation. To test this idea, we fused the chicken GnRHR Ctail to the endogenous murine GnRHR in a transgenic model. The LH surge was blunted, but not blocked in these mice. In contrast, they showed reductions in FSH production, ovarian follicle development, and fertility. Addition of the Ctail altered the nature of agonist-induced calcium signaling required for normal FSH production. The loss of the GnRHR Ctail during mammalian evolution is unlikely to have conferred a selective advantage by enabling the LH surge. The adaptive significance of this specialization remains to be determined.

physiology↗

bioRxiv2021

A human ensemble cell atlas (hECA) enables in data cell sorting

Single-cell omics data can characterize multifaceted features of massive cells and bring significant insights to biomedical researches. The accumulation of single-cell data provides growing resources for constructing atlases for all cells of a human organ or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We proposed a unified information framework enabling seamless cell-centric data assembly and developed a human Ensemble Cell Atlas (hECA) as an instance. hECA version 1.0 assembled scRNA-seq data across multiple studies into one orchestrated data repository. It contains 1,093,299 labeled cells and metadata from 116 published human single-cell studies, covering 38 human organs and 11 systems. We invented three methods of applications based on the cell-centric assembly: "In data" cell sorting enables targeted data retrieval in the full atlas with customizable logic expressions; The "quantitative portraiture" system provides a multi-view presentation of biological entities (organs, cell types, and genes) of multiple granularities; The customizable reference creation allows users to use the cell-centric assembly to generate references for their own cell type annotations. Case studies on agile construction of user-defined sub-atlases and "in data" investigation of CAR-T off-targets in multiple organs showed the great potential of cell-centric atlas assembly.

bioinformatics↗

bioRxiv2021

Mining bacterial NGS data vastly expands the complete genomes of temperate phages

Temperate phages (active prophages induced from bacteria) help control pathogenicity, modulate community structure, and maintain gut homeostasis1. Complete phage genome sequences are indispensable for understanding phage biology. Traditional plaque techniques are inapplicable to temperate phages due to the lysogenicity of these phages, which curb the identification and characterization of temperate phages. Existing in silico tools for prophage prediction usually fail to detect accurate and complete temperate phage genomes2-5. In this study, by a novel computational method mining both the integrated active prophages and their spontaneously induced forms (temperate phages), we obtained 192,326 complete temperate phage genomes from bacterial next-generation sequencing (NGS) data, hence expanded the existing number of complete temperate phage genomes by more than 100-fold. The reliability of our method was validated by wet-lab experiments. The experiments demonstrated that our method can accurately determine the complete genome sequences of the temperate phages, with exact flanking sites (attP and attB sites), outperforming other state-of-the-art prophage prediction methods. Our analysis indicates that temperate phages are likely to function in the evolution of microbes by 1) cross-infecting different bacterial host species; 2) transferring antibiotic resistance and virulence genes; and 3) interacting with hosts through restriction-modification and CRISPR/anti-CRISPR systems. This work provides a comprehensive complete temperate phage genome database and relevant information, which can serve as a valuable resource for phage research.

bioinformatics↗

bioRxiv2021

Mutations in PIKFYVE cause autosomal dominant congenital cataract

Congenital cataract, an ocular disease predominantly occurring within the first decade of life, is one of the leading causes of blindness in children. Through whole exome sequencing of a Chinese family with congenital cataract, we identified a disease-causing mutation (p.G1943E) in PIKFYVE, which affecting the PIP kinase domain of the PIKfyve protein. We demonstrated that heterozygous/homozygous disruption of PIKfyve kinase domain, instead of overexpression of PIKFYVEG1943E in zebrafish mimicked the cataract defect in human patients, suggesting that haploinsufficiency, rather than dominant-negative inhibition of PIKfyve activity caused the disease. Phenotypical analysis of pikfyve zebrafish mutants revealed that loss of Pikfyve caused aberrant vacuolation (accumulation of Rab7+Lc3+ amphisomes) in lens cells, which was significantly alleviated by treatment with the V-ATPase inhibitor bafilomycin A1 (Baf-A1). Collectively, we identified PIKFYVE as a novel causative gene for congenital cataract and demonstrated the potential application of Baf-A1 in treatment of congenital cataract.

genomics↗