Mechanism of action of the nitrosoureas: formation of 1,2-(diguanosin-7-yl) ethane from the reaction of BCNU (1,3-bis-[2-chloroethyl]-1-nitrosourea) with guanosine

A crosslinked dinucleoside, 1,2-(diguanosin-7-yl) ethane, has been isolated from the reaction of guanosine with the antitumor agent, BCNU. The formation of this product suggests that DNA crosslinking, which may be responsible for the cytotoxicity of BCNU, could occur through such dinucleosides.     

Linear viscoelastic properties of the vertex model for epithelial tissues

Epithelial tissues act as barriers and, therefore, must repair themselves, respond to environmental changes and grow without compromising their integrity. Consequently, they exhibit complex viscoelastic rheological behavior where constituent cells actively tune their mechanical properties to change the overall response of the tissue, e.g., from solid-like to fluid-like. Mesoscopic mechanical properties of epithelia are commonly modeled with the vertex model. While previous studies have predominantly focused on the rheological properties of the vertex model at long time scales, we systematically studied the full dynamic range by applying small oscillatory shear and bulk deformations in both solid-like and fluid-like phases for regular hexagonal and disordered cell configurations. We found that the shear and bulk responses in the fluid and solid phases can be described by standard spring-dashpot viscoelastic models. Furthermore, the solid-fluid transition can be tuned by applying pre-deformation to the system. Our study provides insights into the mechanisms by which epithelia can regulate their rich rheological behavior.     

Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.Subject terms: Cell signalling, Respiratory tract diseases     

黑色素母细胞沿神经的迁移

黑色素细胞是皮肤中的特殊细胞,它产生黑色素,并将其传递给周围的角质形成细胞,从而决定皮肤的颜色等,其来源于黑色素母细胞.因此,了解黑色素母细胞如何迁移至靶点,对改善个体肤色以及诊断和治疗黑色素瘤等都具有重要意义.文章通过对黑色素母细胞沿神经迁移这一模式的过程和相关机制进行综述,希望为个体肤色改善以及黑色素瘤术后复发机制...     

武汉地区硅质磷片金藻的初步研究

1986年11月,在武汉植物所的3个池塘及东湖附近的池塘内采集的标本中,含有大量的具硅质磷片的金藻,共11种,分别隶属于Spiniferomonas, Paraphysomonas, Chrysosphaevella, Mallomonas和Synura 5个属。本文提供了这些藻的硅质磷片、刺及毛的电镜照片。这些藻在中国研究得很少,许多种都是第一次报道,它们中的大多数在世界上其它一些地区也是普遍出现的,有些则毫无疑问地属于世界性分布。     

Eye drop delivery of nano-polymeric micelle formulated genes with cornea-specific promoters

BACKGROUND: This study evaluates the eye drop delivery of genes with cornea-specific promoters, i.e., keratin 12 (K12) and keratocan (Kera3.2) promoters, by non-ionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles (PM) to mouse and rabbit eyes, and investigates the underlying mechanisms. METHODS: Three PM-formulated plasmids (pCMV-Lac Z, pK12-Lac Z and pKera3.2-Lac Z) containing the Lac Z gene for beta-galactosidase (beta-Gal) whose expression was driven by the promoter of either the cytomegalovirus early gene, the keratin 12 gene or the keratocan gene, were characterized by critical micelle concentration (CMC), dynamic light scattering (DLS), and atomic force microscopy (AFM). Transgene expression in ocular tissue after gene delivery was analyzed by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Gal) color staining, 1,2-dioxetane beta-Gal enzymatic activity measurement, and real-time polymerase chain reaction (PCR) analysis. The delivery mechanisms of plasmid-PM on mouse and rabbit corneas were evaluated by EDTA and RGD (arginine-glycine-aspartic acid) peptide. RESULTS: The sizes of the three plasmid-PM complexes were around 150-200 nm with unimodal distribution. Enhanced stability was found for three plasmid-PM formulations after DNase I treatment. After six doses of eye drop delivery of pK12-Lac Z-PM three times a day, beta-Gal activity was significantly increased in both mouse and rabbit corneas. Stroma-specific Lac Z expression was only found in pKera3.2-Lac Z-PM-treated animals with pretreatment by 5 mM EDTA, an opener of junctions. Lac Z gene expression in both pK12-Lac Z-PM and pKera3.2-Lac Z-PM delivery groups was decreased by RGD peptide pretreatment. CONCLUSIONS: Cornea epithelium- and stroma-specific gene expression could be achieved using cornea-specific promoters of keratin 12 and keratocan genes, and the gene was delivered with PM formulation through non-invasive, eye drop in mice and rabbits. The transfection mechanism of plasmid-PM may involve endocytosis and particle size dependent paracellular transport.     

Molecular genetic characterization of rice seed lipoxygenase 3 and assessment of its effects on seed longevity

Lipoxygenases (LOXs) are enzymes involved in lipid peroxidation. Here we reported the identification, molecular and functional characterization of the gene encoding rice (Oryza sativa L.) seed LOX3 (sLOX3). Via a map-based cloning strategy we identified Os03g0700400 as the candidate gene encoding sLOX3. Further functional complementary test and biochemical characterization of the recombinant Os03g0700400 protein verified the identification. The sLOX3 gene was highly expressed in roots, moderately in embryos and very weakly in leaves, leaf sheaths and stems. Transient expression experiment (in rice protoplasts) and subsequent laser confocal microscopic analysis demonstrated that the sLOX3 protein was localized into the cytosol. We next showed that overexpression of sLOX3 in a japonica sLOX3-normal rice cultivar, Wuyunjing 7 accelerated the decrease of seed germination ability when the seeds were routinely stored, which demonstrated that sLOX3 had a negative effect on seed longevity (storability). Meanwhile, an increased occurrence of embryo decay was observed in the same transgenic seeds, suggesting that sLOX3 might negatively affect seed longevity by facilitating colonization of particular seed pathogens. Our result forwarded the understanding of the effects of 9-LOX on rice seed longevity.     

Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2) activation and is involved in resistance to taxol-induced apoptosis

ErbB2 overexpression confers resistance to taxol-induced apoptosis by inhibiting p34(Cdc2) activation. One mechanism is via ErbB2-mediated upregulation of p21(Cip1), which inhibits Cdc2. Here, we report that the inhibitory phosphorylation on Cdc2 tyrosine (Y)15 (Cdc2-Y15-p) is elevated in ErbB2-overexpressing breast cancer cells and primary tumors. ErbB2 binds to and colocalizes with cyclin B-Cdc2 complexes and phosphorylates Cdc2-Y15. The ErbB2 kinase domain is sufficient to directly phosphorylate Cdc2-Y15. Increased Cdc2-Y15-p in ErbB2-overexpressing cells corresponds with delayed M phase entry. Expressing a nonphosphorylatable mutant of Cdc2 renders cells more sensitive to taxol-induced apoptosis. Thus, ErbB2 membrane RTK can confer resistance to taxol-induced apoptosis by directly phosphorylating Cdc2.