ATM and ATR protein kinases play a crucial role in cellular DNA damage responses. The inhibition of ATM and ATR can lead to the abolition of the function of cell cycle checkpoints. In this regard, it is expected that checkpoint inhibitors can serve as sensitizing agents for anti-cancer chemo/radiotherapy. Although several ATM inhibitors have been reported, there are no ATR-specific inhibitors currently available. Here, we report the inhibitory effect of schisandrin B (SchB), an active ingredient of Fructus schisandrae, on ATR activity in DNA damage response. SchB treatment significantly decreased the viability of A549 adenocarcinoma cells after UV exposure. Importantly, SchB treatment inhibited both the phosphorylation levels of ATM and ATR substrates, as well as the activity of the G2/M checkpoint in UV-exposed cells. The protein kinase activity of immunoaffinity-purified ATR was dose-dependently decreased by SchB in vitro (IC50: 7.25 μM), but the inhibitory effect was not observed in ATM, Chk1, PI3K, DNA-PK, and mTOR. The extent of UV-induced phosphorylation of p53 and Chk1 was markedly reduced by SchB in ATM-deficient but not siATR-treated cells. Taken together, our demonstration of the ability of SchB to inhibit ATR protein kinase activity following DNA damage in cells has clinical implications in anti-cancer therapy.

Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGFmediated endothelial migration, capillary tube formation and neovascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis.

T w o actinomycete strains, DF-28 and DF-32T, were isolated from soil samples collected in a deciduous dipterocarp forest in Thailand. They produced longitudinally paired spores on the tips of short sporophores alternately branched from aerial hyphae, and the chemotaxonomic properties of the isolates were the same as those of members of the family Streptosporangiaceae. These phenotypic properties, together with the results of a phylogenetic analysis based on 16s rRNA gene sequences, indicated that these isolates should be assigned to the genus Microbispora. The two isolates showed more than 93% DNA relatedness to each other, but their relatedness to any previously described species of the genus Microbispora was only 4 5 % or less. They were distinguishable from previously described Microbispora spp. b y a combination of physiological and biochemical properties. Therefore, a new species is proposed for these strains, under the name Microbispora corallina sp. nov. The type strain is strain DF-32T ( = JCM 10267T).

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To resolve relationships between members of the family Thermomonosporaceae, phylogenetic analyses using three sets of nucleotide sequences from 16S rDNA, 23S rDNA and the 16S-23S internal transcribed spacer (ITS) were carried out. Nearly all species of the family were included in this study. On the basis of congruous phylogenetic results and chemotaxonomic data, the following proposals are made. First, Actinomadura libanotica, Actinomadura aurantiaca, Actinomadura glomerata and Actinomadura longicatena are transferred to the genus Actinocorallia as Actinocorallia libanotica comb. nov., Actinocorallia aurantiaca comb. nov., Actinocorallia glomerata comb. nov. and Actinocorallia longicatena comb. nov., respectively. All the species of this genus are phylogenetically coherent and of phospholipid type PII (presence of phosphatidylethanolamine), distinguishing them from other Actinomadura species that are of phospholipid type PI (absence of diagnostic phospholipids). Second, Excellospora viridilutea is transferred to the genus Actinomadura as Actinomadura viridilutea comb. nov. As a result of the proposed transfers, the family Thermomonosporaceae now contains four genera Thermomonospora, Actinomadura, Actinocorallia and Spirillospora. The genus Actinocorallia and family Thermomonosporaceae are redescribed.

The incidence of CNS involvement does not decrease in rituximab-era.

A novel and simple method for isolating viable gonadal germ cells (GGCs) was developed in the domestic chicken, Developing gonads were isolated from-day-old chick embryos and cultured for up to hours at. in phosphate bu ered saline without Ca and Mg (PBS [ ]). A discharge of GGCs from the gonad was observed within minutes after introducing the embryonic gonad into PBS [ ], and the number of discharged GGCs increased until hours of incubation. The purity of the GGCs (number of discharged GGCs/total number of discharged cells) was approximately for the initial. hours of incubation and decreased thereafter. The number of discharged GGCs from the left gonad was significantly higher than that from the right gonads in females. Fifty discharged GGCs in PBS [ ] were injected into the blood stream of-day-old chick embryos after staining with PHK fluorescent dye. GGCs exhibiting a fluorescent signal were detected after incubating recipient embryos for days. These results indicate that high-purity, viable GGCs can be collected by simply introducing isolated developing gonads into PBS [ ]. : chicken, gonadal germ cells, isolation, PBS [ ]