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31.
Development of vaccines against pertussis caused by Bordetella holmesii using a mouse intranasal challenge model 下载免费PDF全文
Momoko Saito Keita Odanaka Nao Otsuka Kazunari Kamachi Mineo Watanabe 《Microbiology and immunology》2016,60(9):599-608
Bordetella holmesii is recognized as the third causative agent of pertussis (whooping cough) in addition to Bordetella pertussis and Bordetella parapertussis. Pertussis caused by B. holmesii is not rare around the world. However, to date, there is no effective vaccine against B. holmesii. We examined the protective potency of pertussis vaccines available in Japan and vaccines prepared from B. holmesii. A murine model of respiratory infection was exploited to evaluate protective potency. No Japanese commercial pertussis vaccines were effective against B. holmesii. In contrast, a wBH vaccine and an aBH vaccine prepared from B. holmesii were both protective. Passive immunization with sera from mice immunized with aBH vaccine established protection against B. holmesii, indicating that B. holmesii‐specific serum antibodies might play an important role in protection. Immuno‐proteomic analysis with sera from mice immunized with aBH vaccine revealed that the sera recognized a BipA‐like protein of B. holmesii. An aBH vaccine prepared from a BipA‐like protein‐deficient mutant strain did not have a protective effect against B. holmesii. Taken together, our results suggest that the BipA‐like protein plays an important role in the protective efficacy of aBH vaccine. 相似文献
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Nishiya T Matsumoto K Maekawa S Kajita E Horinouchi T Fujimuro M Ogasawara K Uehara T Miwa S 《The Journal of biological chemistry》2011,286(11):9009-9019
Inducible nitric-oxide synthase (iNOS, NOS2) plays a prominent role in macrophage bactericidal and tumoricidal activities. A relatively large amount of NO produced via iNOS, however, also targets the macrophage itself for apoptotic cell death. To uncover the intrinsic mechanisms of iNOS regulation, we have characterized the SPRY domain- and SOCS box-containing protein 1 (SPSB1), SPSB2, and SPSB4 that interact with the N-terminal region of iNOS in a D-I-N-N-N sequence-dependent manner. Fluorescence microscopy revealed that these SPSB proteins can induce the subcellular redistribution of iNOS from dense regions to diffused expression in a SOCS box-dependent manner. In immunoprecipitation studies, both Elongin C and Cullin-5, components of the multi-subunit E3 ubiquitin ligase, were found to bind to iNOS via SPSB1, SPSB2, or SPSB4. Consistently, iNOS was polyubiquitinated and degraded in a proteasome-dependent manner when SPSB1, SPSB2, or SPSB4 was expressed. SPSB1 and SPSB4 had a greater effect on iNOS regulation than SPSB2. The iNOS N-terminal fragment (residues 1-124 of human iNOS) could disrupt iNOS-SPSB interactions and inhibit iNOS degradation. In lipopolysaccharide-treated macrophages, this fragment attenuated iNOS ubiquitination and substantially prolonged iNOS lifetime, resulting in a corresponding increase in NO production and enhanced NO-dependent cell death. These results not only demonstrate the mechanism of SPSB-mediated iNOS degradation and the relative contributions of different SPSB proteins to iNOS regulation, but also show that iNOS levels are sophisticatedly regulated by SPSB proteins in activated macrophages to prevent overproduction of NO that could trigger detrimental effects, such as cytotoxicity. 相似文献
34.
van Oers RF van Rietbergen B Ito K Hilbers PA Huiskes R 《Biomechanics and modeling in mechanobiology》2011,10(5):663-670
Bone formation responds to mechanical loading, which is believed to be mediated by osteocytes. Previous theories assumed that loading stimulates osteocytes to secrete signals that stimulate bone formation. In computer simulations this 'stimulatory' theory successfully produced load-aligned trabecular structures. In recent years, however, it was discovered that osteocytes inhibit bone formation via the protein sclerostin. To reconcile this with strain-induced bone formation, one must assume that sclerostin secretion decreases with mechanical loading. This leads to a new 'inhibitory' theory in which loading inhibits osteocytes from inhibiting bone formation. Here we used computer simulations to show that a sclerostin-based model is able to produce a load-aligned trabecular architecture. An important difference appeared when we compared the response of the stimulatory and inhibitory models to loss of osteocytes, and found that the inhibitory pathway prevents the loss of trabeculae that is seen with the stimulatory model. Further, we demonstrated with combined stimulatory/inhibitory models that the two pathways can work side-by-side to achieve a load-adapted bone architecture. 相似文献
35.
Malay Choudhury Takahiro Oku Shoji Yamada Masaharu Komatsu Keita Kudoh Takao Itakura Seiichi Ando 《Central European Journal of Biology》2011,6(4):545-557
Apolipoproteins such as apolipoprotein (apo) A-I, apoA-IV, and apoE are lipid binding proteins synthesized mainly in the liver
and the intestine and play an important role in the transfer of exogenous or endogenous lipids through the circulatory system.
To investigate the mechanism of lipid transport in fish, we have isolated some novel genes of the apoA-I family, apoIA-I (apoA-I isoform) 1–11, from Japanese eel by PCR amplification. Some of the isolated genes of apoIA-I corresponded to 28kDa-1 cDNAs which had already been deposited into the database and encoded an apolipoprotein with molecular
weight of 28 kDa in the LDL, whereas others seemed to be novel genes. The structural organization of all apoIA-Is consisted of four exons separated by three introns. ApoIA-I10 had a total length of 3232 bp, whereas other genes except for apoIA-I9 ranged from 1280 to 1441 bp. The sequences of apoIA-Is at the exon-intron junctions were mostly consistent with the consensus sequence (GT/AG) at exon-intron boundaries, whereas
the sequences of 3′ splice acceptor in intron 1 of apoIA-I1-7 were (AC) but not (AG). The deduced amino acid sequences of all apoIA-Is contained a putative signal peptide and a propeptide
of 17 and 5 amino acid residues, respectively. The mature proteins of apoIA-I1-3, 7, and 8 consisted of 237 amino acids, whereas
those of apoIA-I4-6 consisted of 239 amino acids. The mature apoIA-I10 sequence showed 65% identity to amino acid sequence
of apoIA-I11 which was associated with an apolipoprotein with molecular weight of 23 kDa in the VLDL. All these mature apoIA-I
sequences satisfied the common structural features depicted for the exchangeable apolipoproteins such as apoA-I, apoA-IV,
and apoE but apoIA-I11 lacked internal repeats 7, 8, and 9 when compared with other members of apoA-I family. Phylogenetic
analysis showed that these novel apoIA-Is isolated from Japanese eel were much closer to apoA-I than apoA-IV and apoE, suggesting
new members of the apoA-I family. 相似文献
36.
Masashi Iwanaga Yuka Adachi Koudai Uchiyama Keita Tsukui Susumu Katsuma Hideki Kawasaki 《In vitro cellular & developmental biology. Animal》2014,50(9):792-796
Bombyx mori ovary-derived BmN4 cells have been successfully adapted to a commercial serum-free medium (SFM; SF900-II) by gradually reducing the serum-containing TC-100 medium content from 100 to 0% (v/v). The BmN4 cells adapted to the SFM (BmN-SFM) adhered strongly to the culture flask and showed altered cell morphology. The BmN-SFM was subcultured 200 times, and the population doubling time was 4.70 d. Infection studies showed that BmN-SFM cells were easily susceptible to B. mori nucleopolyhedrovirus (BmNPV), and both the multiplication of budded virus and the promoter activity of the polyhedrin gene in BmN-SFM cells were almost the same as those in BmN4 cells before adaptation. Additionally, mouse interleukin-3 expressed by a recombinant BmNPV was normally secreted and modified with N-linked glycans in BmN-SFM cells. These findings indicate that BmN-SFM is particularly useful for a BmNPV-based baculovirus expression vector system with serum-free conditions. 相似文献
37.
Keiichi Hata Naohiro Kobayashi Keita Sugimura Weihua Qin Deis Haxholli Yoshie Chiba Sae Yoshimi Gosuke Hayashi Hiroki Onoda Takahisa Ikegami Christopher
B Mulholland Atsuya Nishiyama Makoto Nakanishi Heinrich Leonhardt Tsuyoshi Konuma Kyohei Arita 《Nucleic acids research》2022,50(21):12527
Ubiquitin-like with PHD and RING finger domain-containing protein 1 (UHRF1)-dependent DNA methylation is essential for maintaining cell fate during cell proliferation. Developmental pluripotency-associated 3 (DPPA3) is an intrinsically disordered protein that specifically interacts with UHRF1 and promotes passive DNA demethylation by inhibiting UHRF1 chromatin localization. However, the molecular basis of how DPPA3 interacts with and inhibits UHRF1 remains unclear. We aimed to determine the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. Induced α-helices in DPPA3 upon binding of UHRF1 PHD contribute to stable complex formation with multifaceted interactions, unlike canonical ligand proteins of the PHD domain. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibited binding to UHRF1 and its chromatin localization. Our results provide structural insights into the mechanism and specificity underlying the inhibition of UHRF1 by DPPA3. 相似文献
38.
Mouse Models for Assessing the Protective Efficacy of Lactobacillus gasseri SBT2055 against Helicobacter suis Infection Associated with the Development of Gastric Mucosa‐Associated Lymphoid Tissue Lymphoma 下载免费PDF全文
39.
Kai H Hirashima K Matsuda O Ikegami H Winkelmann T Nakahara T Iba K 《Journal of experimental botany》2012,63(11):4143-4150
Reduced levels of trienoic fatty acids (TAs) in chloroplast membranes induce thermotolerance in several plant species, but the underlying mechanisms remain unclear. TA peroxidation in plant cell membranes generates cytotoxic, TA-derived compounds containing α,β-unsaturated carbonyl groups. The relationship between low TA levels and the amounts of cytotoxic TA-derived compounds was examined using thermotolerant transgenic cyclamen (Cyclamen persicum Mill.) with low TA contents. Changes in the levels of the cytotoxic TA-derived acrolein (ACR), methyl vinyl ketone (MVK), (E)-2-hexenal, 4-hydroxy-2-nonenal, and malondialdehyde were analysed in the leaf tissues of wild-type (WT) and thermotolerant transgenic cyclamen under heat stress. Levels of ACR and MVK in the WT increased in parallel with the occurrence of heat-induced tissue damage, whereas no such changes were observed in the thermotolerant transgenic lines. Furthermore, exogenous ACR and MVK infiltrated into leaves to concentrations similar to those observed in heat-stressed WT leaves caused similar disease symptoms. These results suggest that thermotolerance in transgenic cyclamen depends on reduced production rates of ACR and MVK under heat stress, due to the low level of TAs in these plants. 相似文献
40.