Biology subjects

Ke, J.

Publications and source records attributed to Ke, J..

26 records · Page 2Linked to original sources

bioRxiv2023

A Plant Flavonol Rescues a Pathogenic Mutation Associated with Kinesin in Neurons

KIF1A, a microtubule-based motor protein responsible for axonal transport, is linked to a group of neurological disorders known as KIF1A-associated neurological disorder (KAND). Current therapeutic options for KAND are limited. Here, we introduced the clinically relevant KIF1A(R11Q) variant into the C. elegans homolog UNC-104, resulting in uncoordinated animal behaviors. Through genetic suppressor screens, we identified intragenic mutations in UNC-104s motor domain that rescued synaptic vesicle localization and coordinated movement. We showed that two suppressor mutations partially recovered motor activity in vitro by counteracting the structural defect caused by R11Q at KIF1As nucleotide-binding pocket. We found that supplementation with fisetin, a plant flavonol, improved KIF1A(R11Q) worms movement and morphology. Notably, our biochemical and single-molecule assays revealed that fisetin directly restored the ATPase activity and processive movement of human KIF1A(R11Q) without affecting wild-type KIF1A. These findings suggest fisetin as a potential intervention for enhancing KIF1A(R11Q) activity and alleviating associated defects in KAND.

cell biology↗

bioRxiv2023

African swine fever virus I196L is a virulence determinant and its deletant induces robust protection in Domestic pig

The worldwide pandemic of African swine fever virus (ASFV) has a profound impact on the global pig industry. ASFV is a complex multilayered structure and the functions of unknown genes are being revealed. Here we deleted I196L from virulent ASFV SY18 with different length and obtained two recombinant viruses. The replication efficiency of the two recombinant viruses were similar but significantly lower than parental SY18. The pigs all survived the two recombinant viruses with 106.0TCID50 except one pig occurred sudden death and the suvived pigs all resisted the challenge without fever after intramuscularly injecting a lethal dose (102.0TCID50) of ASFV SY18. The recombinant viruses induced a strong anti-p54 humoral immune response. Meanwhile, the pigs also inevitably appeared moderate to high viremia throughout the observation period and presented a gradually downward trend. The results show that deleting I196L gene is a potential and effective vaccine that protects pigs from ASFV. IMPORTANCEThe worldwide outbreak of African swine fever (ASF) cannot be effectively prevented due to no availably commercial vaccine. Many different types of vaccine candidates are researched and reported, which is a hopeful trend to develop safety and efficacy vaccine. Here we report on an unknown functional gene, I196L, which affects the virulence and replication of ASFV. When I196L was deleted from ASFV SY18, the recombinant virus decreased virulence and resisted the challenge of parental strain. This is a novel, effective, potential live attenuated vaccine (LAVs) for ASF.

immunology↗

bioRxiv2022

Three-dimensional molecular architecture of mouse organogenesis

Mammalian embryos have sophisticated cell organizations that are orchestrated by molecular regulation at cellular and tissue level. It has recently been appreciated that the cells that make up the animal body themselves harbor significant heterogeneity in the context of both cellular and particularly spatial dimension. However, current spatial transcriptomics profiling of embryonic tissues either lack three-dimensional representation or are restricted to limited depth and organs. Here, we reported a holistic spatial transcriptome atlas of all major organs at embryonic day 13.5 of mouse embryo and delineated a 3D rendering of the molecular regulation of embryonic patterning. By integrating with corresponding single-cell transcriptome data, the spatial organogenesis atlas provides rich molecular annotation of the dynamic organ nature, spatial cellular interaction, embryonic axes and divergence of cell fates underlying mammalian development, which would pave the way for precise organ-engineering and stem-cell based regenerative medicine.

developmental biology↗

bioRxiv2022

MADET: A Manually Curated Knowledgebase for Microbiomic Effects on Efficacy and Toxicity of Anticancer Treatments

A plethora of studies have reported the associations between microbiota and multiple diseases, leading to at least four databases to demonstrate microbiota-disease associations, i.e., gutMDisorder, mBodyMap, GMrepo and Amadis. Moreover, gut microbiota also mediates drug efficacy and toxicity, whereas a comprehensive database to elucidate the microbiota-drug associations is lacking. Here we report an open-access knowledgebase, MADET (Microbiomics of Anticancer Drug Efficacy and Toxicity), which harbors 453 manually annotated microbiota-drug associations from 24 papers. MADET provides user-friendly functions allowing users to freely browse, search, and download the data conveniently from the database. Users can customize their search filters in MADET using different types of keywords, including bacterial name (e.g., Akkermansia muciniphila), anticancer treatment (e.g., anti-PD-1 therapy) or cancer type (e.g., lung cancer) with different types of experimental evidence of microbiota-drug association and causation. We have also enabled user submission to further enrich the data document in MADET. The MADET database is freely available at https://www.madet.info. We anticipate that MADET will serve as a useful resource for a better understanding of the microbiota-drug associations and facilitate the future development of novel biomarkers and live biotherapeutic products for anticancer therapies.

microbiology↗

bioRxiv2022

Physiological and molecular mechanisms regulated mesophyll conductance under severe drought in water-saving drought-resistant rice

Water-saving and drought-resistant rice (WDR) is a new type of rice varieties. It plays an important role in responding to drought with high yield and has been widely planted in central China at present. High photosynthetic production potential caused by high mesophyll conductance (gm) is the main factor promoted high yield formation in drought for WDR. But little is known about physiological and molecular mechanisms regulated gm in drought for WDR. Therefore, WDR cultivar HY73 and drought-sensitive cultivar HLY898 were used for comparative studies with three irrigation regimes before applying severe drought treatment at heading to create different differential individuals of photosynthetic potential and gm. The results showed that cultivar HY73 had lower up-regulation different expression genes (DEGs) than cultivar HLY898 in drought at transcriptional level. Conversely, DEGs of down-regulation was higher in cultivar HY73 than cultivar HLY898. In addition, 3071 DEGs were clustered in 3 modules named Midnightblue (734 DEGs), Blue (921 DEGs), and Turquoise (1416 DEGs) in severe drought merged three irrigation regimes and both cultivars, which the modules had significant correlational relationship with gm based on weighted gene co-expression network analysis (P<0.05). Only DEGs in midnightblue module were enriched in photosynthesis process and positively regulated gm (P<0.05). The main biological process were photosynthesis (GO:0015979), light harvesting in photosystem I (GO:0009768), reductive pentose-phosphate cycle (GO:0019253), protein-chromophore linkage (GO:0018298), photosynthetic electron transport in photosystem I (GO:0009773), and photosystem II repair (GO:0010206). These results indicate that gm and energy distribution in PSI and PSII systems could synergistic effect photosynthetic production potential in severe drought for rice plants. In the modules, the 18 most highly connected hub genes were screened using co-expression networks method. RT-PCR analysis indicated that CSP41B, PGLP1A, LHCA5, and GSTU6 genes had a similar variation trend with gm among treatments for both cultivar. LHCA5 and CSP41B genes were significantly up-regulated in HY73 compared with HLY898 in drought (P<0.05). And the both genes locates in thylakoid membrane in photosystems. Therefore, LHCA5 and CSP41B genes could be key genes to synergistically manage gm and energy distribution in photosystems. Our results provide some new physiological and molecular mechanisms regulated gm in severe drought for WDR.

physiology↗

bioRxiv2022

Long-term two-photon imaging of spinal cord in freely behaving mice

The spinal cord is critical to the perception of peripheral information under sensory-guided motor behaviors in health and disease. However, the cellular activity underlie spinal cord function in freely behaving animals is not clear. Here, we developed a new method for imaging the spinal cord at cellular and subcellular resolution over weeks under naturalistic conditions. The method involves an improved surgery to reduce spinal movement, and the installation of a miniaturized two-photon microscope to obtain high-resolution imaging in moving mice. In vivo calcium imaging demonstrated that dorsal horn neurons show a sensorimotor program-dependent synchronization and heterogeneity under distinct cutaneous stimuli in behaving mice. The long-term imaging of sensory neurons revealed that in the spinal cord, healthy mice demonstrated stereotyped responses. However, in a neuropathic pain model, plasticity changes and neuronal sensitization were observed. We provide a practical method to study the function of spinal cord on sensory perception and disorders in freely behaving mice.

neuroscience↗

bioRxiv2021

An AAV-ie based Vaccine effectively protects against SARS-CoV-2 and Circulating Variants

Prophylactic vaccines against SARS-CoV-2 have been extensively developed globally to overcome the COVID-19 pandemic. However, recently emerging SARS-CoV-2 variants B.1.1.7 and B.1.351 limit the vaccine protection effects and successfully escape antibody cocktail treatment. Herein, based on our previously engineered adeno-associated viral (AAV) vector, AAV-ie, and systematic immunogen screening, we developed an AAV-ie-S1 vaccine with thermostability, high efficiency, safety, and single-dose vaccination advantage. Importantly, the AAV-ie-S1 immune sera efficiently neutralize B.1.1.7 and B.1.351, indicating a potential to circumvent the spreading of SARS-CoV-2.

microbiology↗

bioRxiv2019

Time-dependent Canonical Correlation Analysis for Multilevel Time Series

Canonical Correlation Analysis is a technique in multivariate data analysis for finding linear projections that maximize the correlation between two groups of variables. The correlations are typically defined without accounting for the serial correlations between observations, a typical setting for time series data. To understand the coupling dynamics and temporal variations between the two time-varying sources, we introduce the time-dependent canonical correlation analysis (TDCCA), a method for inferring time-dependent canonical vectors from multilevel time series data. A convex formulation of the problem is proposed, which leverages the singular value decomposition (SVD) characterization of all solutions of the CCA problem. We use simulated datasets to validate the proposed algorithm. Moreover, we propose a novel measure, canonical correlation variation as another way to assess the dynamic pattern of brain connections and we apply it to a real resting state fMRI dataset to study the aging effects on brain connectivity. Additionally, we explore our proposed method in a task-related fMRI to detect the temporal dynamics due to different motor tasks. We show that, compared to extant methods, the TDCCA-based approach not only detect temporal changes but also improves feature extraction. Together, this paper contributes broadly to new computational methodologies in understanding multilevel time series.

neuroscience↗