Biology subjects

Kong, F.

Publications and source records attributed to Kong, F..

32 records · Page 2Linked to original sources

bioRxiv2023

SoyDNGP: A Web-Accessible Deep Learning Framework for Genomic Prediction in Soybean Breeding

Soybean is a globally significant crop, playing a vital role in human nutrition and agriculture. Its complex genetic structure and wide trait variation, however, pose challenges for breeders and researchers aiming to optimize its yield and quality. Addressing this biological complexity requires innovative and accurate tools for trait prediction. In response to this challenge, we have developed SoyDNGP, a Convolutional Neural Networks (CNN)-based model that offers significant advancements in the field of soybean trait prediction. Compared to existing methods, such as DeepGS and DNNGP, SoyDNGP boasts a distinct advantage due to its lower parameter volume and superior predictive accuracy. Through rigorous performance comparison, including prediction accuracy and model complexity, SoyDNGP consistently outperformed its counterparts. Furthermore, it effectively predicted complex traits with remarkable precision, demonstrating robust performance across different sample sizes and trait complexities. We also tested the versatility of SoyDNGP across multiple crop species, including Cotton, Maize, Rice, and Tomato. Our results showed its consistent and comparable performance, emphasizing SoyDNGPs potential as a versatile tool for genomic prediction across a broad range of crops. To enhance its accessibility to users without extensive programming experience, we have designed a user-friendly web server, available at http://xtlab.hzau.edu.cn/SoyDNGP. The server provides two primary features: Trait Lookup, offering users the ability to access pre-existing trait predictions for over 500 soybean accessions, and Trait Prediction, allowing for the upload of VCF files for trait estimation. By providing a high-performing, accessible tool for trait prediction and genomic analysis, SoyDNGP opens up new possibilities in the quest for efficient and optimized soybean breeding.

plant biology↗

bioRxiv2023

Effect of growing regions on morphological characteristics, protein nutrition, rumen degradation and molecular structures of various whole-plant silage corn cultivars

Little information exists on the variation of morphological characteristics, nutritional value, ruminal degradability, and molecular structural makeup of diverse whole-plant silage corn (WPSC) cultivars among different growing regions. This study investigated the between-regions discrepancies in five widely used WPSC cultivars in China (FKBN, YQ889, YQ23, DK301 and ZD958) in terms of 1) morphological characteristics; 2) crude protein (CP) chemical profile; 3) Cornell Net Carbohydrate and Protein System (CNCPS) CP subfractions; 4) in situ CP degradation kinetics; and 5) CP molecular structures. Our results revealed that significant difference were observed on growing region and WPSC cultivar interaction for all estimated morphological characteristics (P < 0.001), CP chemical profile (P < 0.001), CNCPS subfractions (P < 0.001) and CP molecular structural features (P < 0.05). Except ear weight (P = 0.18), all measured morphological characteristics varied among different growing regions (P < 0.001). Besides, WPSC cultivars planted in different areas had remarkably different (P < 0.01) CP chemical profiles and CNCPS subfractions. All spectral parameters of protein primary structure of WPSC differed (P < 0.05) due to the various growing regions, except amide II area (P = 0.28). Finally, the area ratio of amide I to II was negatively correlated with the contents of soluble CP ({delta} = -0.66; P = 0.002), CP ({delta} = - 0.61; P = 0.006), non-protein N ({delta} = -0.56; P = 0.004) and acid detergent insoluble CP ({delta} = - 0.43; P = 0.008), in conjunction with positively correlated with moderately degradable CP (PB1;{delta} = 0.58; P = 0.01). In conclusion, the current study suggested that even for the same WPSC cultivar, the morphological characteristics, protein nutritional values and rumen degradability significantly varied among different grown regions due to distinguished molecular structures. Author summaryAs the major roughage source, whole plant silage corn plays an essential role in ruminant feed industry. The quality and quantity of it largely influenced by environmental and climate conditions except genetic factors. However, there was limited information to systematically analyze whole plant silage corn from morphological characteristics, nutritional components, rumen degradation to its inherent molecular structures. Thus, this study was conducted to investigate the discrepancies of various silage-corn cultivars grown in different regions from internal structure to phenotype based novel technology - fourier transform infrared spectroscopy.

biochemistry↗

bioRxiv2023

The unknown lipids project: harmonized methods improve compound identification and data reproducibility in an inter-laboratory untargeted lipidomics study

Untargeted lipidomics allows analysis of a broader range of lipids than targeted methods and permits discovery of unknown compounds. Previous ring trials have evaluated the reproducibility of targeted lipidomics methods, but inter-laboratory comparison of compound identification and unknown feature detection in untargeted lipidomics has not been attempted. To address this gap, five laboratories analyzed a set of mammalian tissue and biofluid reference samples using both their own untargeted lipidomics procedures and a common chromatographic and data analysis method. While both methods yielded informative data, the common method improved chromatographic reproducibility and resulted in detection of more shared features between labs. Spectral search against the LipidBlast in silico library enabled identification of over 2,000 unique lipids. Further examination of LC-MS/MS and ion mobility data, aided by hybrid search and spectral networking analysis, revealed spectral and chromatographic patterns useful for classification of unknown features, a subset of which were highly reproducible between labs. Overall, our method offers enhanced compound identification performance compared to targeted lipidomics, demonstrates the potential of harmonized methods to improve inter-site reproducibility for quantitation and feature alignment, and can serve as a reference to aid future annotation of untargeted lipidomics data.

systems biology↗

bioRxiv2023

Force-regulated spontaneous conformational changes of integrins α5β1 and αVβ3

Force can modulate the properties and functions of macromolecules by inducing conformational changes, such as coiling/uncoiling, zipping/unzipping, and folding/unfolding. Here we compared force-modulated bending/unbending of two purified integrin ectodomains, 5{beta}1 and V{beta}3, using single-molecule approaches. Similar to previously characterized mechano-sensitive macromolecules, the conformation of 5{beta}1 is determined by a threshold head-to-tail tension, suggesting a canonical energy landscape with a deep energy well that traps the integrin in the bent state until sufficient force tilts the energy landscape to accelerate transition to the extended state. By comparison, V{beta}3 exhibits bi-stability even without force and can spontaneously transition between the bent and extended conformations in a wide range of forces without energy supplies. Molecular dynamics simulations revealed consecutive formation and disruption of 7 hydrogen bonds during V{beta}3 bending and unbending, respectively. Accordingly, we constructed an energy landscape with hexa-stable intermediate states to break down the energy barrier separating the bent and extended states into smaller ones, making it possible for the thermal agitation energy to overcome them sequentially and to be accumulated and converted into mechanical work required for V{beta}3 to bend against force. Our study elucidates the different inner workings of 5{beta}1 and V{beta}3 at the sub-molecular level, sheds lights on how their respectively functions are facilitated by their distinctive mechano-sensitivities, helps understand their signal initiation processes, and provides critical concepts and useful design principles for engineering of protein-based biomechanical nanomachines.

biophysics↗

bioRxiv2022

Distinct function of SPL genes in age-related resistance in Arabidopsis

In plants, age-related resistance (ARR) refers to a gain of disease resistance during shoot or organ maturation. ARR associated with vegetative phase change, a transition from juvenile to adult stage, is a widespread agronomic trait affecting resistance against multiple pathogens. How innate immunity in a plant is differentially regulated during successive stages of shoot maturation is unclear. In this work, we found that Arabidopsis thaliana showed ARR against its bacterial pathogen Pseudomonas syringae pv. tomato DC3000 during vegetative phase change. The timing of the ARR activation was associated with a temporal drop of miR156 level. A systematic inspection of the loss- and gain-of-function mutants of 11 SPL genes revealed that a subset of SPL genes, notably SPL2, SPL10, and SPL11, activated ARR in adult stage. The immune function of SPL10 was independent of its role in morphogenesis. Furthermore, the SPL10 mediated an age-dependent augmentation of the salicylic acid (SA) pathway partially by direct activation of PAD4. Disrupting SA biosynthesis or signaling abolished the ARR against Pto DC3000. Our work demonstrated that the miR156-SPL10 module in Arabidopsis is deployed to operate immune outputs over developmental timing. SignificanceAge-associated change of immunity is a widespread phenomenon in animals and plants. How organisms integrate immune maturation into a developmental clock is a fundamental question. Heterochronic microRNAs are key regulators of developmental timing. We found that a conserved heterochronic microRNA (miRNA) in Arabidopsis, microRNA156, regulates the timing of age-related resistance associated with a transition from the juvenile to the adult vegetative phase. The coordination between developmental maturation and gain of disease resistance is achieved through miR156-controlled SPL transcription factors with distinct functions. A subset of SPL transcription factors promoted resistance by directly activating key genes in defense signaling. This work bridges the knowledge gap between vegetative development and age-related resistance. Pinpointing mechanisms of the developmental regulation on immunity may pave a way for unlocking the age limit on plant immunity and lay a foundation to applications in the precision agriculture.

plant biology↗

bioRxiv2022

NR5A2 connects genome activation to the first lineage segregation in early mouse development

After fertilization, zygotic genome activation (ZGA) marks the beginning of the embryonic program for a totipotent embryo, which further gives rise to the pluripotent embryonic lineages and extraembryonic trophectoderm after the first lineage commitment. While much has been learned about pluripotency regulation, how ZGA is connected to the pluripotency commitment in early embryos remains elusive. Here, we investigated the role of nuclear receptor 1 family transcription factors (TFs) in mouse pre-implantation embryos, whose motifs are highly enriched in accessible chromatin at the 2-cell (2C) to 8-cell (8C) stages after ZGA. We found NR5A2, an NR TF highly induced upon ZGA, is required for early development, as both the knockdown and knockout of Nr5a2 from 1C embryos led to morula arrest. While the zygotic genome was largely activated at the 2C stage, 4-8C-specific gene activation (mid-preimplantation activation) was substantially impaired. Genome-wide chromatin binding and RNA-seq analyses showed NR5A2 preferentially regulates its binding targets including a subset of key pluripotency genes (i.e., Nanog, Pou5f1, and Tdgf1). Finally, NR5A2-occupied sites at the 2C and 8C stages predominantly reside in accessible B1 elements where its motif is embedded. Taken together, these data identify NR5A2 as a key regulator that connects ZGA to the first lineage segregation in early mouse development.

developmental biology↗

bioRxiv2022

LSR Targets YAP to Modulate Intestinal Paneth Cell Differentiation

Lipolysis-stimulated lipoprotein receptor (LSR) is a multi-functional protein that is best known for its roles in assembly of epithelial tricellular tight junctions and hepatic clearance of lipoproteins. Here, we investigated whether LSR contributes to intestinal epithelium homeostasis and pathogenesis of intestinal disease. By using multiple conditional deletion mouse models and ex vivo cultured organoids, we find that LSR elimination in intestinal stem cells results in disappearance of Paneth cell without affecting the differentiation of other cell lineages. Mechanistic studies reveal that LSR deficiency increases abundance and nuclear localization of YAP by modulating its phosphorylation and proteasomal degradation. Using gain- and loss-of-function studies we show that LSR protects against necrotizing enterocolitis through enhancement of Paneth cell differentiation in small intestinal epithelium. Thus, this study identifies LSR as an upstream negative regulator of YAP activity, an essential factor for Paneth cell differentiation, and a potential novel therapeutic target for inflammatory bowel disease.

cell biology↗

bioRxiv2022

A SNP affects Wnt4 expression in endometrial stroma, with antagonistic implications for pregnancy, endometriosis and reproductive cancers

The common human single nucleotide polymorphism rs3820282 is associated with multiple phenotypes ranging from gestational length to likelihood of endometriosis and ovarian cancer and can thus serve as a paradigm for a highly pleiotropic genetic variant. Pleiotropy makes it challenging to assign specific causal roles to particular genetic variants. Deleterious mutations in multifunctional genes may cause either the co-occurrence of multiple disorders in the same individuals (i.e., syndromes), or be repeatedly associated with a variety of disorders in a population. Moreover, the adverse effects can occur in combination with advantages in other traits, maintaining high frequencies of deleterious alleles in the population. To reveal the causal role of this specific SNP, we investigated the molecular mechanisms affected by rs3820282 in mice. We have shown previously that rs3820282 introduces a high affinity estrogen receptor 1 binding site at the Wnt4 locus. Having introduced this nucleotide substitution into the homologous site of the mouse genome by CRISPR/Cas 9 we show that this change causes a specific upregulation of Wnt4 transcription in the endometrial stromal cells during the preovulatory estrogen peak in late proestrus. Transcriptomic analysis of the whole uterus reveals broad systemic effects on uterine gene expression, including downregulation of proliferation and induction of many progesterone-regulated pro-implantation genes. The effect on proliferation is limited to the luminal epithelium, whereas other effects involve the uterine stromal compartment. We suggest that in the uterus, these changes could contribute to increased permissiveness to embryo invasion. Yet in other estrogen-responsive tissues, the same changes potentially lead to decreased resistance to invasion by cancer cells and endometriotic foci. A single molecular effect of rs3820282 on Wnt4 expression may thus underlie the various associated phenotypic effects.

genetics↗

bioRxiv2021

Neuroplastin genetically interacts with Cadherin 23 and the encoded isoform Np55 is sufficient for cochlear hair cell function and hearing

Mammalian hearing involves the mechanoelectrical transduction (MET) of sound-induced fluid waves in the cochlea. Essential to this process are the specialised sensory cochlear cells, the inner (IHCs) and outer hair cells (OHCs). While genetic hearing loss is highly heterogeneous, understanding the requirement of each gene will lead to a better understanding of the molecular basis of hearing and also to therapeutic opportunities for deafness. The Neuroplastin (Nptn) gene, which encodes two protein isoforms Np55 and Np65, is required for hearing, and homozygous loss-of-function mutations that affect both isoforms lead to profound deafness in mice. Here we have utilised several distinct mouse models to elaborate upon the spatial, temporal, and functional requirement of Nptn for hearing. While we demonstrate that both Np55 and Np65 are present in cochlear cells, characterisation of a Np65-specific mouse knockout shows normal hearing thresholds indicating that Np65 is functionally redundant for hearing. In contrast, we find that Nptn-knockout mice have significantly reduced maximal MET currents and MET channel open probabilities in mature OHCs, with both OHCs and IHCs also failing to develop fully mature basolateral currents. Furthermore, comparing the hearing thresholds and IHC synapse structure of Nptn-knockout mice with those of mice that lack Nptn only in IHCs and OHCs shows that the majority of the auditory deficit is explained by hair cell dysfunction, with abnormal afferent synapses contributing only a small proportion of the hearing loss. Finally, we show that continued expression of NEUROPLASTIN in OHCs of adult mice is required for membrane localisation of Plasma Membrane Ca2+ ATPase 2 (PMCA2), which is essential for hearing function. Moreover, Nptn haploinsufficiency phenocopies Atp2b2 (encodes PMCA2) mutations, with heterozygous Nptn-knockout mice exhibiting hearing loss through genetic interaction with the Cdh23ahl allele. Together, our findings provide further insight to the functional requirement of Neuroplastin for mammalian hearing. Author SummarySensorineural hearing loss, caused by problems with sensory cells in the cochlea or the auditory nerve, is the most common type of hearing loss. Mutations in Neuroplastin have already been implicated in deafness in mice. We have used mutant mouse models to investigate where Neuroplastin is expressed in the cochlea and its function. When mice do not express a functioning copy of Neuroplastin they have disruptions to the primary sensory synapse. We show that although synaptic disruption contributes to the loss of hearing function it is not the primary cause. Instead, continued expression of Neuroplastin is needed to maintain the localisation of Plasma Membrane Ca2+ ATPase 2 channels which help regulate calcium flow. We have also shown that two types of NEUROPLASTIN protein (isoforms) are both expressed within the cochlea, although only one of these isoforms needs to be expressed for normal hearing. Finally, we also demonstrate that the hearing loss caused by the absence of Neuroplastin is made worse when combined with a common mutation within a gene called Cadherin 23 (Cdh23ahl). This is an important finding as although there are currently no human patients with an identified NEUROPLASTIN mutation, it may be involved in human deafness in combination with other mutations.

neuroscience↗

bioRxiv2021

Selenium in wheat from farming to food

Selenium (Se) plays an important role in human health. Approximately 80% of the worlds population does not consume enough Se which recommended by WHO (World Health Organization). Wheat is an important staple food and Se source for most people in the world. This article summarizes literatures about Se from 1936 to 2020 to investigate Se in wheat farming soil, wheat, and its derived foods. Se fortification and the recommended Se level in wheat were also discussed. Results showed that Se contents in wheat farming soil, grain, and its derived foods around the world were 3.8-552 (mean, 220.99), 0-8,270 (mean, 347.30), and 15-2,372 (mean, 211.86) g{middle dot}kg-1, respectively. Adopting suitable agronomic measures could effectively realize Se fortification in wheat. The contents in grain, flour, and its derived foods could be improved from 93.94 to 1,181.92, 73.06 to 1,007.75, and 86.90 to 587.61 g{middle dot}kg-1 in average after leaf Se fertilizer application in the field. There was a significant positive correlation between Se content in farming soil and grain, and it was extremely the same between foliar Se fertilizer concentration rate and grain Se increased rate. The recommended Se fortification level in cultivation of wheat in China, India, and Spain was 18.53-23.96, 2.65-3.37, and 3.93-9.88 g{middle dot}hm-2 respectively. Milling processing and food type could greatly affect Se content of wheat derived food and should be considered seriously to meet peoples Se requirement by wheat. TOC graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/452805v3_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@c75842org.highwire.dtl.DTLVardef@173722dorg.highwire.dtl.DTLVardef@4cfc97org.highwire.dtl.DTLVardef@5b23d0_HPS_FORMAT_FIGEXP M_FIG C_FIG

plant biology↗

bioRxiv2021

Pulsed Focal ultrasound as a non-invasive method to deliver exosomes in the brain/stroke

Exosomes, a component of extracellular vesicles are shown to carry important small RNAs, mRNAs, protein, and bioactive lipid from parent cells and are found in most biological fluids. Investigators have demonstrated the importance of mesenchymal stem cells (MSCs) derived exosomes in repairing stroke lesions. However, exosomes from endothelial progenitor cells (EPCs) have not been tested in any stroke model nor has there been an evaluation of whether these exosomes target/home to areas of pathology. Targeted delivery of IV administered exosomes has been a great challenge and a targeted delivery system is lacking to deliver naive (unmodified) exosomes from EPCs to the site of interest. Pulsed focused ultrasound (pFUS) is being used for therapeutic and experimental purposes. There has not been any report showing the use of pulsed low-intensity pFUS to deliver exosomes to the site of interest in models of stroke. In this proof of principle study, we have shown different parameters of pFUS to deliver exosomes in the intact and stroke brain with or without IV administration of nanobubbles. The study results showed that administration of nanobubbles is detrimental to the brain structures (micro bleeding and white matter destruction) at peak negative pressure (PNP) of >0.25 MPa, despite enhanced delivery of IV administered exosomes. However, without nanobubbles, pFUS PNP = 1 to 2 MPa enhances the delivery of exosomes in the stroke area without altering the brain structures.

neuroscience↗

bioRxiv2020

BMSCs differentiated into neurons, astrocytes and oligodendrocytesalleviatedthe inflammation and demyelination of EAE mice models

Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Previous studies have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2 neurons marker, GFAP astrocytes marker, and MBP oligodendrocytes marker expression to evaluate whether BMSCs can differentiate. The effect of BMSCs transplantation on inflammatory cell invasion and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining. Inflammatory factors expression was detected by ELISA and RT-qPCR. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro. In addition, BMSCs transplant improved the survival rate and weight, and reduced neurological function scores and disease incidence of EAE mice. Moreover, BMSCs transplant alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the expression levels of pro-inflammatory factors TNF-, IL-1{beta} and IFN-{gamma}, and up-regulated the expression levels of anti-inflammatory factors IL-10 and TGF-{beta}. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.

neuroscience↗

bioRxiv2019

An oomycete effector impairs autophagy in evolutionary distant organisms and favors host infection

An arsenal of effector proteins from plant pathogenic Phytophthora species manipulates their host from inside the cells. Phytophthora parasitica produces the effector AVH195 during an initial, biotrophic phase of infection. The protein transiently impairs plant immune-associated hypersensitive cell death in Nicotiana. ATG8 Interaction Motifs in the protein indicate that the effector targets the autophagic core machinery. We selected a photosynthetic microalga with a single copy ATG8 gene as an alternative model to dissect AVH195-induced autophagic perturbation. AVH195 slows down autophagic flux in Chlamydomonas reinhardtii thus promoting the accumulation of cargo-rich vesicles. In yeast, membrane-associated AVH195 interacts with ATG8 from Chlamydomonas and with different ATG8 isoforms from Arabidopsis thaliana. The overexpression of Avh195 in Arabidopsis promotes growth of both infecting P. parasitica and Hyaloperonospora arabidopsidis, an obligate biotroph. To our knowledge, this report provides first evidence that an oomycete effector non-selectively targets ATG8 in different organisms from the green lineage to slow down autophagic flux for infection.

plant biology↗

bioRxiv2018

Molecular Mechanisms Governing Shade Responses in Maize

Light is one of the most important environmental factors affecting plant growth and development. Plants use shade avoidance and shade tolerance strategies to adjust their growth and development thus increase their success in the competition for incoming light. To investigate the mechanism of shade responses in maize (Zea mays), we examined the anatomical and transcriptional dynamics of the early shade response in seedlings of the B73 inbred line. Transcriptome analysis identified 912 differentially expressed genes, including genes involved in light signaling, auxin responses, and cell elongation pathways. Grouping transcription factor family genes and performing enrichment analysis identified multiple types of transcription factors that are differentially regulated by shade and predicted putative core genes responsible for regulating shade avoidance syndrome. For functional tests, we ectopically over-expressed ZmHB53, a type II HD-ZIP transcription factor gene significantly induced by shade, in Arabidopsis thaliana. Transgenic Arabidopsis plants overexpressing ZmHB53 exhibited narrower leaves, earlier flowering, and enhanced expression of shade-responsive genes, suggesting that ZmHB53 participates in the regulation of shade responses in maize. This study increases our understanding of the regulatory network of the shade response in maize and provides a useful resource for maize genetics and breeding.\n\nHighlightOur findings not only increase the understanding of the regulatory network of the shade avoidance in maize, and also provide a useful resource for maize genetics and breeding.

plant biology↗