Protective Effect of Piceatannol Against Cerebral Ischaemia–Reperfusion Injury Via Regulating Nrf2/HO-1 Pathway In Vivo and Vitro

Neurochemical Research - Piceatannol is a natural plant-derived compound with protective effects against cardiovascular diseases. However, its effect on cerebral ischaemia–reperfusion injury...     

The Neurotrophic Effects and Mechanism of Action for FK1706 in Neurorrhaphy Rat Models and SH-SY5Y Cells

FK1706 is a novel non-immunosuppressive immunophilin ligand with neurotrophic activity and exerts its neurotrophic effect through NGF. The present study aimed to elaborate on the neurotrophic activity and the mechanism of action of FK1706 in end-to-side neurorrhaphy rats and SH-SY5Y cells. In the regenerating nerves of neurorrhaphy rats, FK1706 increased the thickness of myelin sheath and the level of nerve regeneration-related proteins. The mechanism of action of FK1706 on neurite regrowth was elucidated in vitro by incubating SH-SY5Y cells in different conditions (Control, NGF, FK1706, NGF?+?FK1706, NGF?+?FK1706?+?geldanamycin). Under the conditions where NGF was used, the phosphorylation level of major proteins (Raf-1 and ERK) in the Ras/Raf/MAPK/ERK signaling pathway related to SH-SY5Y cell proliferation was significantly enhanced following the application of FK1706. The number of viable cells, cell viability and neurite length of SH-SY5Y cells was maximal when NGF and FK1706 were used simultaneously. The binding level of HSP90 and Raf-1 in FK1706 group was the highest. These results indicated that FK1706 could significantly promote nerve regeneration after neurorrhaphy. The putative mechanism of action stated that FK1706 could promote the binding of HSP90 and Raf-1, make Raf-1 continue to be activated, thereby affecting key proteins in the Ras/Raf/MAPK/ERK signaling pathway related to the neurotrophic effects of NGF to promote the proliferation and neurite regrowth of nerve cells.

     

Plasticity of symbiont acquisition in new recruits of the massive coral Platygyra daedalea under ocean warming and acidification

Coral Reefs - Symbiosis establishment is a milestone in the life cycles of most broadcast-spawning corals; however, it remains largely unknown how initial symbiont infection is affected by ocean...     

High-content screening of diterpenoids from Isodon species as autophagy modulators and the functional study of their antiviral activities

Cell Biology and Toxicology - Autophagy is a conserved lysosomal degradation process, and abnormal autophagy has been associated with various pathological processes, e.g., neurodegeneration,...     

Feedback regulation of coronary artery disease susceptibility gene ADTRP and LDL receptors LDLR/CD36/LOX-1 in endothelia cell functions involved in atherosclerosis

A high level of low-density lipoprotein cholesterol (LDL) is one of the most important risk factors for coronary artery disease (CAD), the leading cause of death worldwide. However, a low concentration of LDL may be protective. Genome-wide association studies revealed that variation in ADTRP gene increased the risk of CAD. In this study, we found that a low concentration of oxidized-LDL induced the expression of ADTRP. Further analyses showed that knockdown of the expression of LDL receptor genes LDLR, CD36, or LOX-1 significantly downregulated ADTRP expression, whereas overexpression of LDLR/CD36/LOX-1 markedly increased ADTRP expression through the NF-κB pathway. Like ADTRP, LDLR, CD36 and LOX-1 were all involved in endothelial cell (EC) functions relevant to the initiation of atherosclerosis. Downregulation of LDLR/CD36/LOX-1 promoted monocyte adhesion to ECs and transendothelial migration of monocytes by increasing expression of ICAM-1, VCAM-1, E-selectin and P-selectin, decreased EC proliferation and migration, and increased EC apoptosis, thereby promoting the initiation of atherosclerosis. Opposite effects were observed with the overexpression of ADTRP and LDLR/CD36/LOX-1 in ECs. Interestingly, through the NF-κB and AKT pathways, overexpression of ADTRP significantly upregulated the expression of LDLR, CD36, and LOX-1, and knockdown of ADTRP expression significantly downregulated the expression of LDLR, CD36, and LOX-1. These data suggest that ADTRP and LDL receptors LDLR/CD36/LOX-1 positively regulate each other, and form a positive regulatory loop that regulates endothelial cell functions, thereby providing a potential protective mechanism against atherosclerosis. Our findings provide a new molecular mechanism by which deregulation of ADTRP and LDLR/CD36/LOX-1 promote the development of atherosclerosis and CAD.     

Divergent DNA methylation contributes to duplicated gene evolution and chilling response in tea plants

The tea plant (Camellia sinensis) is a thermophilic cash crop and contains a highly duplicated and repeat-rich genome. It is still unclear how DNA methylation regulates the evolution of duplicated genes and chilling stress in tea plants. We therefore generated a single-base-resolution DNA methylation map of tea plants under chilling stress. We found that, compared with other plants, the tea plant genome is highly methylated in all three sequence contexts, including CG, CHG and CHH (where H = A, T, or C), which is further proven to be correlated with its repeat content and genome size. We show that DNA methylation in the gene body negatively regulates the gene expression of tea plants, whereas non-CG methylation in the flanking region enables a positive regulation of gene expression. We demonstrate that transposable element-mediated methylation dynamics significantly drives the expression divergence of duplicated genes in tea plants. The DNA methylation and expression divergence of duplicated genes in the tea plant increases with evolutionary age and selective pressure. Moreover, we detect thousands of differentially methylated genes, some of which are functionally associated with chilling stress. We also experimentally reveal that DNA methyltransferase genes of tea plants are significantly downregulated, whereas demethylase genes are upregulated at the initial stage of chilling stress, which is in line with the significant loss of DNA methylation of three well-known cold-responsive genes at their promoter and gene body regions. Overall, our findings underscore the importance of DNA methylation regulation and offer new insights into duplicated gene evolution and chilling tolerance in tea plants.     

Revisiting the phosphotyrosine binding pocket of Fyn SH2 domain led to the identification of novel SH2 superbinders.

Protein engineering through directed evolution is an effective way to obtain proteins with novel functions with the potential applications as tools for diagnosis or therapeutics. Many natural proteins have undergone directed evolution in vitro in the test tubes in the laboratories worldwide, resulting in the numerous protein variants with novel or enhanced functions. we constructed here an SH2 variant library by randomizing 8 variable residues in its phosphotyrosine (pTyr) binding pocket. Selection of this library by a pTyr peptide led to the identification of SH2 variants with enhanced affinities measured by EC50. Fluorescent polarization was then applied to quantify the binding affinities of the newly identified SH2 variants. As a result, three SH2 variants, named V3, V13 and V24, have comparable binding affinities with the previously identified SH2 triple‐mutant superbinder. Biolayer Interferometry assay was employed to disclose the kinetics of the binding of these SH2 superbinders to the phosphotyrosine peptide. The results indicated that all the SH2 superbinders have two‐orders increase of the dissociation rate when binding the pTyr peptide while there was no significant change in their associate rates. Intriguingly, though binding the pTyr peptide with comparable affinity with other SH2 superbinders, the V3 does not bind to the sTyr peptide. However, variant V13 and V24 have cross‐reactivity with both pTyr and sTyr peptides. The newly identified superbinders could be utilized as tools for the identification of pTyr‐containing proteins from tissues under different physiological or pathophysiological conditions and may have the potential in the therapeutics.     

Cytological and morphology characteristics of natural microsporogenesis within Camellia oleifera

Camellia oleifera is believed to exhibit a complex intraspecific polyploidy phenomenon. Abnormal microsporogenesis can promote the formation of unreduced gametes in plants and lead to sexual polyploidy, so it is hypothesized that improper meiosis probably results in the formation of natural polyploidy in Camellia oleifera. In this study, based on the cytological observation of meiosis in pollen mother cells (PMCs), we found natural 2n pollen for the first time in Camellia oleifera, which may lead to the formation of natural polyploids by sexual polyploidization. Additionally, abnormal cytological behaviour during meiosis, including univalent chromosomes, extraequatorial chromosomes, early segregation, laggard chromosomes, chromosome stickiness, asynchronous meiosis and deviant cytokinesis (monad, dyads, triads), was observed, which could be the cause of 2n pollen formation. Moreover, we confirmed a relationship among the length–width ratio of flower buds, stylet length and microsporogenesis. This result suggested that we can immediately determine the microsporogenesis stages by phenotypic characteristics, which may be applicable to breeding advanced germplasm in Camellia oleifera.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-01002-5.     

Microcella flavibacter sp. nov., isolated from marine sediment,and reclassification of Chryseoglobus frigidaquae,Chryseoglobus indicus,and Yonghaparkia alkaliphila as Microcella frigidaquae comb. nov., Microcella indica nom. nov., and Microcella alkalica nom. nov.

A novel Gram-staining positive, aerobic, rod-shaped, non-motile and yellow-pigmented actinobacterium, designated strain WY83^T, was isolated from a marine sediment of Indian Ocean. Strain WY83^T grew optimally at 30–35 °C, pH 7–8 and with 0–3% (w/v) NaCl. The predominant menaquinones were MK-10, MK-11 and MK-12, and the major fatty acids were C_19:1 ω9c/C19:1 ω11c, anteiso-C_15:0, C_17:0 3OH, and iso-C_16:0. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and one unidentified glycolipid. The cell-wall peptidoglycan contained lysine as a diamino acid. The DNA G?+?C content was 72.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences and ninety-two bacterial core genes indicated that strain WY83^T formed an evolutionary lineage with Chryseoglobus frigidaquae JCM 14730^T, Chryseoglobus indicus CTD02-10-2^T, Yonghaparkia alkaliphila JCM 15138^T, Microcella alkaliphila DSM 18851^T and Microcella putealis DSM 19627^T within the radiation enclosing members of the family Microbacteriaceae. All pairwise percentage of conserved proteins between strain WY83^T and the closely related phylogenetic neighbors were greater than 65%. The average nucleotide identity and in silico DNA–DNA hybridization values were both below the thresholds used for the delineation of a new species. On the basis of the evidence presented, strains WY83^T, Y. alkaliphila JCM 15138^T, C. frigidaquae JCM 14730^T, M. alkaliphila DSM 18851^T and M. putealis DSM 19627^T should belong to different species of the same genus. Strain WY83^T represents a novel species of the genus Microcella, for which the name Microcella flavibacter sp. nov. is proposed. The type strain is WY83^T (=?KCTC 39637^T?=?MCCC 1A07099^T). Furthermore, Chryseoglobus frigidaquae, Chryseoglobus indicus, and Yonghaparkia alkaliphila were reclassified as Microcella frigidaquae comb. nov., Microcella indica nom. nov., and Microcella alkalica nom. nov., respectively.

     

LncRNA H19 rs4929984 Variant is Associated with Coronary Artery Disease Susceptibility in Han Chinese Female Population

Biochemical Genetics - Long non-coding RNAs (lncRNAs) have been reported to play an important role in cardiovascular diseases. The present study aimed to investigate the levels of lncRNA H19 in...