TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation

Given that exosomes mediate intercellular communication by delivering cellular components to recipient cells or tissue, they have the potential to be engineered to deliver therapeutic payloads. However, the regulatory mechanism of exosome secretion is poorly understood. In addition, mitochondrial components have been found in exosomes, suggesting communication between mitochondria and exosomes. However, the molecular mechanism of the mitochondria and vesicle interaction remains unclear. Here, we showed that mitochondrial thioredoxin 2 (TRX2) decreased exosome concentrations and inhibited HCT116 cell migration. Coimmunoprecipitation/mass spectrometry (Co-IP/MS) showed that TRX2 interacted with Rab35. TRX2 and Rab35 bound to each other at their N-terminal motifs and colocalized on mitochondria. Furthermore, TRX2 induced Rab35 degradation, resulting in impaired exosome secretion. Additionally, Rab35 mediated the suppressive effects of TRX2 on cell migration, and TRX2 suppressed cell migration through exosomes. Taken together, this study first found an interaction between TRX2 and Rab35. These results revealed a new role for TRX2 in the regulation of exosome secretion and cell migration and explained the upstream regulatory mechanism of Rab35. Furthermore, these findings also provide new molecular evidence for communication between mitochondria and vesicles.     

Structural and Molecular Kinetic Features of Activities of DNA Polymerases

DNA polymerases catalyze DNA synthesis during the replication, repair, and recombination of DNA. Based on phylogenetic analysis and primary protein sequences, DNA polymerases have been categorized into seven families: A, B, C, D, X, Y, and RT. This review presents generalized data on the catalytic mechanism of action of DNA polymerases. The structural features of different DNA polymerase families are described in detail. The discussion highlights the kinetics and conformational dynamics of DNA polymerases from all known polymerase families during DNA synthesis.     

Sogatella furcifera Saliva Mucin-like Protein Is Required for Feeding and Induces Rice Defences

The white-backed planthopper (WBPH), Sogatella furcifera, is one of the most important piercing-sucking pests of rice (Oryza sativa) in Asia. Mucin-like salivary protein (SFMLP) is highly expressed in the salivary glands of WBPH, which plays an important role in WBPH feeding. In this study, WBPH injected with dsSFMLP had difficulty in sucking phloem sap from rice plants, which significantly reduced their food intake, weight, and survival. In contrast, the knockdown of the SFMLP gene had only a marginal effect on the survival of WBPH fed an artificial diet. Further studies showed that silencing SFMLP resulted in the short and single-branched salivary sheaths secretion and less formation of salivary flanges in rice. These data suggest that SFMLP is involved in the formation of the salivary sheath and is essential for feeding in WBPH. Overexpression of the SFMLP gene in rice plants promoted the feeding of WBPH, whereas silencing the gene in rice plants significantly decreased WBPH performance. Additionally, it was found that overexpression of SFMLP in rice plants elicited the signalling pathway of SA (salicylic acid) while suppressing JA (jasmonic acid); in contrast, silencing of the SFMLP gene in rice plants showed the opposite results. This study clarified the function of SFMLP in WBPH feeding as well as mediating rice defences.     

The β2-Subunit (AMOG) of Human Na+, K+-ATPase Is a Homophilic Adhesion Molecule

The β₂ subunit of Na⁺, K⁺-ATPase was originally identified as the adhesion molecule on glia (AMOG) that mediates the adhesion of astrocytes to neurons in the central nervous system and that is implicated in the regulation of neurite outgrowth and neuronal migration. While β₁ isoform have been shown to trans-interact in a species-specific mode with the β₁ subunit on the epithelial neighboring cell, the β₂ subunit has been shown to act as a recognition molecule on the glia. Nevertheless, none of the works have identified the binding partner of β₂ or described its adhesion mechanism. Until now, the interactions pronounced for β₂/AMOG are heterophilic cis-interactions. In the present report we designed experiments that would clarify whether β₂ is a cell–cell homophilic adhesion molecule. For this purpose, we performed protein docking analysis, cell–cell aggregation, and protein–protein interaction assays. We observed that the glycosylated extracellular domain of β₂/AMOG can make an energetically stable trans-interacting dimer. We show that CHO (Chinese Hamster Ovary) fibroblasts transfected with the human β₂ subunit become more adhesive and make large aggregates. The treatment with Tunicamycin in vivo reduced cell aggregation, suggesting the participation of N-glycans in that process. Protein–protein interaction assay in vivo with MDCK (Madin-Darby canine kidney) or CHO cells expressing a recombinant β₂ subunit show that the β₂ subunits on the cell surface of the transfected cell lines interact with each other. Overall, our results suggest that the human β₂ subunit can form trans-dimers between neighboring cells when expressed in non-astrocytic cells, such as fibroblasts (CHO) and epithelial cells (MDCK).     

Hematopoietic–Mesenchymal Signals Regulate the Properties of Mesenchymal Stem Cells

It is well known that the properties of hematopoietic stem/progenitor cells (HSCs), such as their self-renewal ability and multipotency, are maintained through interactions with mesenchymal stem/stromal cells (MSCs). MSCs are rare cells that are present in the bone marrow and are useful for clinical applications due to their functional ability. To obtain the necessary number of cells, MSCs must be cultured to expand, but this causes a remarkable decrease in stem cell properties, such as multipotency and proliferation ability. In this study, we show that the c-Mpl signal, which is related to the maintenance of hematopoietic stem cells, has an important effect on the proliferation and differentiation ability of MSCs. Utilizing a co-culture system comprising MSCs and HSCs, it is suggested that signaling from hematopoietic cells to MSCs supports cell proliferation. Interestingly, the enhanced proliferation ability of the HSCs was decreased in c-Mpl knock-out HSCs (c-Mpl-KO). In addition, the MSCs co-cultured with c-Mpl-KO HSCs had reduced MSC marker expression (PDGFRa and Sca-1) compared to the MSCs co-cultured with c-Mpl-wild-type HSCs. These results suggest that a hematopoietic–mesenchymal signal exists, and that the state of the HSCs is important for the stability of MSC properties.     

水文土壤学理论及其应用研究进展

围绕水文土壤学的基本理论和核心科学问题,从地球关键区理论出发,介绍了水文土壤学的基本理论框架、水文土壤学所能填补的知识鸿沟,并回顾了水文土壤学在农业、流域管理、面源污染、湿地保护和环境政策制定以及土壤传递函数等方面的应用,最后对水文土壤学的发展和应用做了展望。     

Revealing the Immune Heterogeneity between Systemic Lupus Erythematosus and Rheumatoid Arthritis Based on Multi-Omics Data Analysis

The pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are greatly influenced by different immune cells. Nowadays both T-cell receptor (TCR) and B-cell receptor (BCR) sequencing technology have emerged with the maturity of NGS technology. However, both SLE and RA peripheral blood TCR or BCR repertoire sequencing remains lacking because repertoire sequencing is an expensive assay and consumes valuable tissue samples. This study used computational methods TRUST4 to construct TCR repertoire and BCR repertoire from bulk RNA-seq data of both SLE and RA patients’ peripheral blood and analyzed the clonality and diversity of the immune repertoire between the two diseases. Although the functions of immune cells have been studied, the mechanism is still complicated. Differentially expressed genes in each immune cell type and cell–cell interactions between immune cell clusters have not been covered. In this work, we clustered eight immune cell subsets from original scRNA-seq data and disentangled the characteristic alterations of cell subset proportion under both SLE and RA conditions. The cell–cell communication analysis tool CellChat was also utilized to analyze the influence of MIF family and GALECTIN family cytokines, which were reported to regulate SLE and RA, respectively. Our findings correspond to previous findings that MIF increases in the serum of SLE patients. This work proved that the presence of LGALS9, PTPRC and CD44 in platelets could serve as a clinical indicator of rheumatoid arthritis. Our findings comprehensively illustrate dynamic alterations in immune cells during pathogenesis of SLE and RA. This work identified specific V genes and J genes in TCR and BCR that could be used to expand our understanding of SLE and RA. These findings provide a new insight inti the diagnosis and treatment of the two autoimmune diseases.     

Interactions between hotspots and the Southwest Indian Ridge during the last 90 Ma:Implications on the formation of oceanic plateaus and intra-plate seamounts

This study investigates the relationship between the hotspot-ridge interaction and the formation of oceanic plateaus and seamounts in the Southwest Indian Ocean.We first calculated the relative distance between the Southwest Indian Ridge (SWIR) and relevant hotspots on the basis of models of plate reconstruction,and then calculated the corresponding excess magmatic anomalies of the hotspots on the basis of residual bathymetry and Airy isostasy.The results reveal that the activities of the Marion hotspot can...