Biology subjects

cao, y.

Publications and source records attributed to cao, y..

6 recordsLinked to original sources

bioRxiv2025

A Gm6AG-binding protein from Vibrio cholerae.

Most known modification-dependent restriction endonucleases target 5-methylcytosine, only a few N6-methyladenine (6mA)-dependent restriction endonucleases have been well-characterized, and the majority of them recognize the G6mATC motif (e.g., DpnI, HHPV4I). Here, we report the identification of a novel 6mA-dependent DNA-binding protein from Vibrio cholerae, VchI, which specifically recognizes the G6mAG motif. VchI contains a winged helix (wH) domain that is homologous to the wH domain in DpnI. However, several key residues involved in 6mA recognition differ between VchI and DpnI, which may contribute to the discrepancy in their recognition specificities. These findings advance our understanding of prokaryotic 6mA modification diversity and the 6mA recognition mechanism of the wH domain, while simultaneously providing an innovative tool for epigenetic research.

biochemistry↗

bioRxiv2022

Reduced mesophyll conductance by cell wall thickening and chloroplasts decreasing driven the decline of photosynthesis under sole NH4+ supply

The relationship between nitrogen (N) sources and photosynthetic capacity of leaf differs between species. However, the leaf anatomical variabilities related to photosynthesis (A) of shrubs under different forms of N remain imperfectly known. Here, Lonicera Japonica (a shrub) was grown hydroponically in the presence of three forms of N (sole NH4+, 50%/50% NH4+/NO3- and sole NO3-). A and photosynthetic N use efficiency significantly decreased under sole NH4+ supply, in parallel with down-regulated stomatal conductance (gs), mesophyll conductance (gm), and electron transfer rate (J). Up to the total A decline of 41.28% in sole NH4+ supply (compare with sole NO3-), the gm attributed to 60.3% of the total limitations. Besides, the decreased internal air space explained the increase of gas-phase resistance, and the increased liquid-phase resistance in sole NH4+ supply was ascribed to the thicker cell wall thickness (Tcw) and decreased chloroplasts exposed surface area per unit leaf area (Sc/S). The discrepancy of Sc/S could be interpreted by the altered chloroplasts numbers and the distance between adjacent chloroplasts (Dchl-chl). These results indicate the alteration of Tcw and chloroplast numbers were the main causes of the difference in gm in coping with varied N sources. HighlightCell wall and chloroplast variability determining the mesophyll conductance under different nitrogen forms

physiology↗

bioRxiv2021

An enzyme-based system for the extraction of small extracellular vesicles from plants

Plant-derived nanovesicles (NVs) and extracellular vesicles (EVs) are considered to be the next generation of nanocarrier platforms for biotherapeutics and drug delivery. However, EVs exist not only in the extracellular space, but also within the cell wall. Due to the limitation of isolation methods, the extraction efficiency is low, resulting in the waste of a large number of plants, especially rare and expensive medicinal plants.There are few studies comparing EVs and NVs. To overcome these challenges, we proposed and validated a novel method for the isolation of plant EVs by degrading the plant cell wall with enzymes to release the EVs in the cell wall, making it easier for EVs to break the cell wall barrier and be collected. We extracted EVs from the roots of Morinda officinalis by enzymatic degradation(MOEVs) and nanoparticles by grinding method (MONVs) as a comparison group. The results showed smaller diameter and higher yield of MOEVs.Both MOEVs and MONVs were readily absorbed by endothelial cells without cytotoxicity and promoted the expression of miR-155. The difference is that the promotion of miR-155 by MOEVs is dose-effective. More importantly, MOEVs and MONVs are naturally characterized by bone enrichment. These results support that EVs in plants can be efficiently extracted by enzymatic cell wall digestion and also confirm the potential of MOEVs as therapeutic agents and drug carriers.

pharmacology and toxicology↗

bioRxiv2021

The Lyme Disease agent co-opts adiponectin receptor-mediated signaling in its arthropod vector

Adiponectin-mediated pathways contribute to mammalian homeostasis; however, little is known about adiponectin and adiponectin receptor signaling in arthropods. In this study, we demonstrate that Ixodes scapularis ticks have an adiponectin receptor-like protein (ISARL) but lack adiponectin - suggesting activation by alternative pathways. ISARL expression is significantly upregulated in the tick gut after Borrelia burgdorferi infection suggesting that ISARL-signaling may be co-opted by the Lyme disease agent. Consistent with this, RNA interference (RNAi)-mediated silencing of ISARL significantly reduced the B. burgdorferi burden in the tick. RNA-seq-based transcriptomics and RNAi assays demonstrate that ISARL-mediated phospholipid metabolism by phosphatidylserine synthase I is associated with B. burgdorferi survival. Furthermore, the tick complement C1q-like protein 3 interacts with ISARL, and B. burgdorferi facilitates this process. This study identifies a new tick metabolic pathway that is connected to the life cycle of the Lyme disease spirochete. Significance StatementAdiponectin binds to adiponectin receptors and participates in glucose and lipid metabolism in mammals. In this study, we found that ticks have an adiponectin receptor-like protein but lack adiponectin. Importantly, we demonstrated that the Lyme disease agent, Borrelia burgdorferi, takes advantage of the adiponectin receptor signaling pathway to establish infection in its arthropod vector, Ixodes scapularis. Our study sheds light on the understanding of Borrelia-tick interactions and provides insights into how a human infectious disease agent may evolve to manipulate host metabolism for its own benefits. Understanding this pathway may lead to new ways to interfere with the Borrelia life cycle, and this mechanism may be applicable to additional microbes that are transmitted by ticks, mosquitoes or other arthropods.

microbiology↗

bioRxiv2020

Modeling disease progression in newly diagnosed type 2 diabetes

Type 2 diabetes (T2DM) is a progressive disease, which is primarily characterized by a decline in {beta}-cell function and worsening of insulin resistance. Unfortunately, most interventions (lifestyle, diet, and therapeutic agents) for T2DM only provide a transient restoration of {beta}-cell function and the progression is inevitable once it starts. To understand the natural progression of T2DM, a mechanistic model was developed to quantitatively characterize the dynamic interactions among {beta}-cell function, plasma fasting glucose (PFG), fasting insulin (FI), and the degree of insulin resistance, starting from an early stage of T2DM over up to 8 years. The model was validated using clinical data to optimize the disease parameters. The restoration and deterioration rates of {beta}-cell function were both predicted as 84.5 %/year and 1.10 /year for early stages of T2DM. The model predicted a positive correlation between the initial level of {beta}-cell function at diagnosis and its maximum restoration potential, underscoring the importance of early diagnosis and intervention. After the treatment, {beta}-cell function could be temporarily restored within several months, which has a long-term benefit in glycemic control. The maximal tolerated PFG level that permits {beta}-cell function restoration was predicted to be around 8.33 nM; and the temporal restoration of {beta}-cell function would be unlikely at a PFG level above this threshold. The intrinsic deterioration rates of {beta}-cell function and insulin resistance were both critical factors for long-term glycemic control. In conclusion, our model provides a quantitative analysis of the natural disease progression in T2DM and yields insights into factors that are critical for long-term glycemic control.

pharmacology and toxicology↗

bioRxiv2019

The Structural Basis for Glycerol Permeation by human AQP7

Human glycerol channel AQP7 conducts glycerol release from adipocyte and entry into the cells in pancreatic islets, muscles and kidney tubule, and thus regulate glycerol metabolism in those tissues. Compared with other human aquaglyceroporins, AQP7 shows a less conserved "NPA" motif in the center cavity, and a pair of aromatic residues at Ar/R selectivity filter. To understand the structural basis for the glycerol conductance, we crystallized the human AQP7 and determined the structure at 3.7 [A]. A substrate binding pocket was found near to the Ar/R filter and the bound glycerol molecule stabilized by R229. In vivo functional assay on human AQP7 as well as AQP3 and AQP10 demonstrated strong glycerol transportation activities at physiological condition. The human AQP7 structure reveals a fully closed conformation with its permeation pathway strictly confined by Ar/R filter at the exoplasmic side and the gate at the cytoplasmic side, and the dislocation of the residues at narrowest parts of glycerol pathway in AQP7 play a critical role in controlling the glycerol flux.

molecular biology↗