Biology subjects

Jiang, Y.

Publications and source records attributed to Jiang, Y..

At least 289 records · Page 16Linked to original sources

bioRxiv2023

INTEGRATED GLOBAL CHICKEN REFERENCE PANEL FROM 13,187 CHICKEN GENOMES

Chickens are a crucial source of protein for humans and a popular model animal for bird research. Despite the emergence of imputation as a reliable genotyping strategy for large populations, the lack of a high-quality chicken reference panel has hindered progress in chicken genome research. To address this issue, here we introduce the first phase of the 100 K Global Chicken Reference Panel Project (100 K GCRPP). The project includes 13,187 samples and provides services for varied applications on its website (http://farmrefpanel.com/GCRP/). Currently, two panels are available: a Comprehensive Mix Panel (CMP) for domestication diversity research and a Commercial Breed Panel (CBP) for breeding broilers specifically. Evaluation of genotype imputation quality showed that CMP had the highest imputation accuracy compared to imputation using existing chicken panel in animal SNPAtlas, whereas CBP performed stably in the imputation of commercial populations. Additionally, we found that genome-wide association studies using GCRP-imputed data, whether on simulated or real phenotypes, exhibited greater statistical power. In conclusion, our study indicates that the GCRP effectively fills the gap in high-quality reference panels for chickens, providing an effective imputation platform for future genetic and breeding research.

bioinformatics↗

bioRxiv2023

Structure basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor

The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the receptor extracellular regions and the peptide N-terminus and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa within the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptides recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide receptors.

biophysics↗

bioRxiv2023

E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation

E3 ubiquitin ligases are very important to regulate antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly Influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and H9N2, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-{beta} and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 showed a decreased susceptibility to H9N2 and PR8 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation levels of TBK1 and IRF3, downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator in controlling the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported. IMPORTANCEIAV is a significant zoonotic pathogen that causes infections of the respiratory system. Hosts have evolved multiple strategies to defend against IAV infection. However, not all host proteins play an active defense role. In this study, we found that the E3 ligase ASB3 regulates antiviral immunity by manipulating MAVS stability. Briefly, overexpression of ASB3 degrades MAVS, thereby promoting viral replication. In contrast, ASB3 deletion restores MAVS expression, upregulating IFN-I responses. Additional research revealed that ASB3 mediates the K48-linked polyubiquitination of MAVS at K297, resulting in ASB3 being degraded via the ubiquitin-proteasome pathway. These findings reveal, for the first time, a novel mechanism by which ASB3 negatively regulates antiviral immunity and provides a potential target for anti-IAV drug development.

immunology↗

bioRxiv2023

High-resolution awake mouse fMRI at 14 Tesla

High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion induced artifacts. Using a 14T scanner, high-resolution fMRI enabled brain- wide functional mapping of visual and vibrissa stimulation at 100x100x200{micro}m resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detected using a randomized stimulation paradigm. This early BC activation indicated a learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas. Significance StatementThis awake mouse fMRI platform was developed by implementing an advanced implantable radiofrequency (RF) coil scheme, which simultaneously served as a headpost to secure the mouse head during scanning. A thorough acclimation method was used to accustom animals to the MRI environment minimizing motion induced artifacts. The ultra-high spatial resolution (100x100x200{micro}m) BOLD fMRI enabled the brain-wide mapping of activated visual and vibrissa systems during sensory stimulation in awake mice, including association cortices, e.g. anterior cingulate cortex and retrosplenial cortex, for high order sensory processing. Also, the activation of barrel cortex at 2 s prior to the air-puff indicated a learned anticipation of awake mice under continuous training of the repetitive vibrissa stimulation.

neuroscience↗

bioRxiv2023

AhR ligands from LGG metabolites promote piglet intestinal ILC3 activation and IL-22 secretion to inhibit PEDV infection

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationship between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG (LGG) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3 cells and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor exerts its influence on various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, fostering their growth and development, suggesting a broad impact of AhR on intestinal health. In conclusion, our study demonstrates the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock.

immunology↗

bioRxiv2023

A comprehensive overview and benchmarking analysis of fast algorithms for genome-wide association studies

Genome-wide association studies (GWAS) are a ubiquitous tool for identifying genetic variants associated with complex traits in structured populations. During the past 15 years, many fast GWAS algorithms based on a state-of-the-art model, namely the linear mixed model, have been published to cope with the rapidly growing data size. In this study, we provide a comprehensive overview and benchmarking analysis of 33 commonly used GWAS algorithms. Key mathematical techniques implemented in different algorithms were summarized. Empirical data analysis with 12 selected algorithms showed differences regarding the identification of quantitative trait loci (QTL) in several plant species. The performance of these algorithms evaluated in 10,800 simulated data sets with distinct population size, heritability and genetic architecture revealed the impact of these parameters on the power of QTL identification and false positive rate. Based on these results, a general guide on the choice of algorithms for the research community is proposed.

genetics↗

bioRxiv2023

Spatially resolved molecular and cellular atlas of the mouse brain

A comprehensive atlas of genes, cell types, and their spatial distribution across a whole mammalian brain is fundamental for understanding function of the brain. Here, using snRNA-seq and Stereo-seq techniques, we generated a mouse brain atlas with spatial information for 308 cell clusters with single-cell resolution involving over 6 million cells as well as for 29,655 genes. We have identified new astrocyte clusters, and demonstrated that distinct cell clusters exhibit preference for cortical subregions. In addition, we identified 155 genes exhibiting regional specificity in the brainstem, and 513 long non-coding RNA exhibited regional specificity in the adult brain. Parcellation of brain regions based on spatial transcriptomic information showed large overlap with that by traditional method. Furthermore, we have uncovered 411 transcription factor regulons with spatiotemporal specificity during development. Thus, our study has discovered genes and regulon with spatiotemporal specificity, and provided a high-resolution spatial transcriptomic atlas of the mouse brain.

neuroscience↗

bioRxiv2023

Bi-parental graph strategy to represent and analyze hybrid plant genomes

Hybrid plants are universally existed in wild and often exhibit greater performance of complex traits compared with their parents and other selfing plants. This phenomenon, known as heterosis, has been extensively applied in plant breeding for decades. However, the process of decoding hybrid plant genomes has seriously lagged due to the challenges in their genome assembling and the lack of proper methods to further represent and analyze them. Here we report the assembly and analysis of two hybrids: an intraspecific hybrid between two maize inbred lines and an interspecific hybrid between maize and its wild relative teosinte, based on the combination of PacBio High Fidelity (HiFi) sequencing and chromatin conformation capture sequencing data. The haplotypic assemblies are well-phased at chromosomal scale, successfully resolving the complex loci with extensive parental structural variations (SVs). By integrating into a bi-parental genome graph, the haplotypic assemblies can facilitate downstream short-reads based SV calling and allele-specific gene expression analysis, demonstrating outstanding advantages over one single linear genome. Our work provides an entire workflow which hopefully can promote the deciphering of the large numbers of hybrid plant genomes, especially those whose parents are unknown or unavailable and help to understand genome evolution and heterosis.

bioinformatics↗

bioRxiv2023

Assessing the capacity of high-resolution commercial satellite imagery for grapevine downy mildew detection and surveillance in New York state

Grapevine downy mildew (GDM), caused by the oomycete Plasmopara viticola, can cause 100% yield loss and vine death under conducive conditions. Growers currently rely on frequent fungicide applications for control, but this practice has led to widespread resistance. Rapid remote detection and surveillance of GDM outbreaks would enable precision pesticide applications to target effective but resistance-prone fungicides where and when most needed, while relying on less resistance-prone protectants elsewhere. High resolution commercial satellite platforms offer the opportunity to track rapidly spreading diseases like GDM over large, heterogeneous fields. Here, we investigate the capacity of PlanetScope (3 m) and SkySat (50 cm) imagery for season-long GDM detection and surveillance. A team of trained scouts rated GDM severity and incidence in two acres of Chardonnay grapevines in Geneva, NY, USA in June-August of 2020, 2021, and 2022. Satellite imagery acquired within 72 hours of scouting was processed to extract single-band reflectance and vegetation indices (VIs). Random forest models trained on spectral bands and VIs derived from both image datasets could classify areas of high and low GDM incidence and severity with maximum accuracies of 0.88 (SkySat) and 0.94 (PlanetScope). However, we do not observe significant differences between VIs of high and low damage classes until late July-early August. We identify cloud cover, image co-registration, and low spectral resolution as key challenges to operationalizing satellite-based GDM surveillance. This work establishes the capacity of spaceborne multispectral sensors to detect late-stage GDM and outlines steps towards incorporating satellite remote sensing in grapevine disease surveillance systems.

plant biology↗

bioRxiv2023

The change of lymphocyte subsets and inflammatory cytokine in BK viruria

BackgroundPolyomavirus BK (BKV) infection as a serious complication after kidney transplantation. The process of infections in kidney transplant recipients is viruria, viremia, and BKVAN. The difference between BK negative and BK viruria in kidney recipients has not been defined. Patients and MethodsWe compared post-transplant lymphocyte subsets blood cytokinesurine cytokines levels of 19 renal transplant outpatients with (BK-positive) or without BK viruria (BK-negative, n=20), and 20 healthy controls (HCs). Group of BK-positive divide into low-(n=4) and high-level (n=15) According to BK viral load (VL).Immune cells including T cells, B cells, and natural killer (NK) cellsinterleukin-2(IL-2),IL-5,IL-6, IL-1{beta}, IL-10, IL-8, IL-17A,IL-4,IL-12P70, interferon-(IFN-), IFN-{gamma},and tumor necrosis factor- (TNF-)were determined by flow cytometry. ResultsBK-positive patients showed higher urine IL-1{beta} (P=0.040), IL-10 (P= 0.010), IFN-{gamma} (P =0.002), and TNF- (P =0.027) than BK-negative patients. Compared with HCs, BK-negative patients had lower urine IL-1{beta} (P=0.04), IL-10 (P=0.01), TNF- (P =0.027) and IFN-{gamma} (P =0.004),suggesting that cytokine expression regulation BK-infection. ConclusionBK-positive renal transplant recipients, especially those with high VL, showed strong inflammatory cytokine responses with increases of urine IL-1{beta}, IL-10, IFN-{gamma}, and TNF-. Our data suggest that monocyte- and Th-2-induced cytokines are involved in the pathogenesis of BKV-associated nephropathy.

immunology↗

bioRxiv2023

Attila and Aetius on the roof: The succession phenomenon in the roof greening area of a primary school in Beijing during the lockdown period of the COVID-19

"Succession" refers to the process of certain species replacing others over time. It is of great significance for understanding the characteristics and evolution of ecosystems. This article compares the changes in school rooftop green areas before and after the COVID-19 epidemic (2019, 2023), and studies the situation of wild grass invading roofs during the three years of the epidemic, as well as the response of original rooftop plants to the invasion. The results showed that: [circled1] invasive weeds were concentrated in 2 families and 4 species, forming a population advantage in most of the invaded planting boxes; [circled2] The succession has had a significant impact on the roof greening area; [circled3] Among the two cultivated plants (Phedimus aizoon (PA) and Sedum sarmentosum (SS)), SS was greatly affected, with the community almost disappearing, while PA was almost unaffected.

ecology↗

bioRxiv2023

Multi-modal microvascular cerebral blood flow velocity mapping with 14T single-vessel MRI and optical microscopy in the mouse brain

In this study, we imaged the same penetrating cortical vessels in a mouse using ultrahigh field single-vessel MRI at 14 T and high-resolution optical microscopy imaging. The optical imaging was performed through a chronic sealed cranial window, while the single-vessel MRI was facilitated by a custom-designed, chronically implanted radiofrequency coil surrounding the window. The MRI and optical imaging were performed sequentially focused on the same penetrating cortical arterioles and surfacing venules within the whisker barrel cortex. With MRI, we obtained high-resolution multi-gradient echo (MGE) images and single-vessel phase contrast (PC) velocity maps. With optical imaging, we acquired microvascular angiograms using 2-Photon Microscopy (2PM) and Optical Coherence Tomography (OCT) and measured the blood flow velocity using Dynamic Light Scattering OCT (DLS-OCT). The MGE images, PC-based MRI velocity maps, OCT angiograms, and DLS-OCT velocity maps were coregistered with the 2PM microvascular angiograms. Using these tools, we cross-validated blood flow velocity in the penetrating cortical arterioles and surfacing venules measured by single-vessel MRI and OCT at rest. Our novel method demonstrates the possibility of combining ultrahigh field single-vessel MRI and high-resolution optical methods (e.g., 2PM and OCT) for studying brain structure and function with single microvessel precision.

bioengineering↗

bioRxiv2023

MIOSTONE: Modeling microbiome-trait associations withtaxonomy-adaptive neural networks

AbstractThe human microbiome, a complex ecosystem of microorganisms inhabiting the body, plays a critical role in human health. Investigating its association with host traits is essential for understanding its impact on various diseases. Although shotgun metagenomic sequencing technologies have produced vast amounts of microbiome data, analyzing such data is highly challenging due to its sparsity, noisiness, and high feature dimensionality. Here we develop MIOSTONE, an accurate and interpretable neural network model for microbiome-disease association that simulates a real taxonomy by encoding the relationships among microbial features. The taxonomy-encoding architecture provides a natural bridge from variations in microbial taxa abundance to variations in traits, encompassing increasingly coarse scales from species to domains. MIOSTONE has the ability to determine whether taxa within the corresponding taxonomic group provide a better explanation in a data-driven manner. MIOSTONE serves as an effective predictive model, as it not only accurately predicts microbiome-trait associations across extensive simulated and real datasets but also offers interpretability for scientific discovery. Both attributes are crucial for facilitating in silico investigations into the biological mechanisms underlying such associations among microbial taxa.

bioinformatics↗

bioRxiv2023

Dynamic encoding of biological motion information in macaque medial superior temporal area

The ability to decipher biological motion information is an essential brain function that develops early in life and is evolutionarily conserved across many species. However, the neuronal encoding of biological motion information remains unclear due to the scarce electrophysiological evidence. In the current study, we tackled this issue by examining whether and how neurons in the monkey medial superior temporal cortex (MST) extract form from biological motion and encode spatial transformations in biological motion. Results revealed that MST neurons are capable of encoding form information and discriminating the horizontal and the vertical mirror transformations of biological motion. More importantly, BM information is dynamically encoded in the modulation strength of evoked spike trains rather than the average firing rate during stimulus presentation. Furthermore, the ability of MST neurons to detect various biological motion features is closely linked with the neuronal selectivity for optic flow patterns.

neuroscience↗

bioRxiv2023

In vivo affinity maturation of murine B cells reprogrammed to express human antibodies

CRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3-most J segments and 5 homology arms complementary to distal V segments. Cells edited in this way to express the HIV-1 broadly neutralizing antibodies 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated recipient mice. 10-1074 variants isolated from these mice bound and neutralized HIV-1 envelope glycoprotein more efficiently than wild-type 10-1074 while maintaining or improving its already low polyreactivity and long in vivo half-life. We further validated this approach by generating substantially broader and more potent variants of the anti-SARS-CoV-2 antibodies ZCB11 and S309. Thus, B cells edited at their native loci affinity mature, facilitating development of broad, potent, and bioavailable antibodies and expanding the potential applications of engineered B cells.

bioengineering↗

bioRxiv2023

Genome-wide transcription and repair maps of Caenorhabditis elegans

Bulky DNA adducts such as those induced by ultraviolet light are removed from the genomes of multicellular organisms by nucleotide excision repair, which occurs through two distinct mechanisms, global repair, requiring the DNA damage recognition-factor XPC (xeroderma pigmentosum complementation group C), and transcription-coupled repair (TCR), which does not. TCR is initiated when elongating RNA polymerase II encounters DNA damage, and thus analysis of genome-wide excision repair in XPC-mutants only repairing by TCR provides a unique opportunity to map transcription events missed by methods dependent on capturing RNA transcription products and thus limited by their stability and/or modifications (5-capping or 3- polyadenylation). Here, we have performed the eXcision Repair-sequencing (XR-seq) in the model organism Caenorhabditis elegans to generate genome-wide repair maps from a wild-type strain with normal excision repair, a strain lacking TCR (csb-1), or one that only repairs by TCR (xpc- 1). Analysis of the intersections between the xpc-1 XR-seq repair maps with RNA-mapping datasets (RNA-seq, long- and short-capped RNA-seq) reveal previously unrecognized sites of transcription and further enhance our understanding of the genome of this important model organism.

genomics↗

bioRxiv2023

The DeMixSC deconvolution framework uses single-cell sequencing plus a small benchmark dataset for improved analysis of cell-type ratios in complex tissue samples

Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we introduce an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using the better-matched, i.e., benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using a benchmark dataset of healthy retinas suggest much-improved deconvolution accuracy. Further analysis of a cohort of 453 patients with age-related macular degeneration supports the broad applicability of DeMixSC. Our findings reveal the impact of technological discrepancy on deconvolution performance and underscore the importance of a well-matched dataset to resolve this challenge. The developed DeMixSC framework is generally applicable for deconvolving large cohorts of disease tissues, and potentially cancer.

bioinformatics↗

bioRxiv2023

Spiral NeuroString: High-Density Soft Bioelectronic Fibers for Multimodal Sensing and Stimulation

Bioelectronic fibers hold promise for both research and clinical applications due to their compactness, ease of implantation, and ability to incorporate various functionalities such as sensing and stimulation. However, existing devices suffer from bulkiness, rigidity, limited functionality, and low density of active components. These limitations stem from the difficulty to incorporate many components on one-dimensional (1D) fiber devices due to the incompatibility of conventional microfabrication methods (e.g., photolithography) with curved, thin and long fiber structures. Herein, we introduce a fabrication approach, "spiral transformation'', to convert two-dimensional (2D) films containing microfabricated devices into 1D soft fibers. This approach allows for the creation of high density multimodal soft bioelectronic fibers, termed Spiral NeuroString (S-NeuroString), while enabling precise control over the longitudinal, angular, and radial positioning and distribution of the functional components. We show the utility of S-NeuroString for motility mapping, serotonin sensing, and tissue stimulation within the dynamic and soft gastrointestinal (GI) system, as well as for single-unit recordings in the brain. The described bioelectronic fibers hold great promises for next-generation multifunctional implantable electronics.

bioengineering↗