TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines

Successful vaccines contain not only protective antigen(s) but also an adjuvant component that triggers innate immune activation and is necessary for their optimal immunogenicity. In the case of DNA vaccines, this consists of plasmid DNA; however, the adjuvant element(s) as well as its intra- and inter-cellular innate immune signalling pathway(s) leading to the encoded antigen-specific T- and B-cell responses remain unclear. Here we demonstrate in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IkappaB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA-activated, TBK1-dependent signalling and the resultant type-I interferon receptor-mediated signalling was required for induction of antigen-specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensor-Toll-like receptor 9 (TLR9) or Z-DNA binding protein 1 (ZBP1, also known as DAI, which was recently reported as a potential B-form DNA sensor). Moreover, bone-marrow-transfer experiments revealed that TBK1-mediated signalling in haematopoietic cells was critical for the induction of antigen-specific B and CD4(+) T cells, whereas in non-haematopoietic cells TBK1 was required for CD8(+) T-cell induction. These data suggest that TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells.     

ATP drives lamina propria T(H)17 cell differentiation

Interleukin (IL)-17-producing CD4(+) T lymphocytes (T(H)17 cells) constitute a subset of T-helper cells involved in host defence and several immune disorders. An intriguing feature of T(H)17 cells is their selective and constitutive presence in the intestinal lamina propria. Here we show that adenosine 5'-triphosphate (ATP) that can be derived from commensal bacteria activates a unique subset of lamina propria cells, CD70(high)CD11c(low) cells, leading to the differentiation of T(H)17 cells. Germ-free mice exhibit much lower concentrations of luminal ATP, accompanied by fewer lamina propria T(H)17 cells, compared to specific-pathogen-free mice. Systemic or rectal administration of ATP into these germ-free mice results in a marked increase in the number of lamina propria T(H)17 cells. A CD70(high)CD11c(low) subset of the lamina propria cells expresses T(H)17-prone molecules, such as IL-6, IL-23p19 and transforming-growth-factor-beta-activating integrin-alphaV and -beta8, in response to ATP stimulation, and preferentially induces T(H)17 differentiation of co-cultured naive CD4(+) T cells. The critical role of ATP is further underscored by the observation that administration of ATP exacerbates a T-cell-mediated colitis model with enhanced T(H)17 differentiation. These observations highlight the importance of commensal bacteria and ATP for T(H)17 differentiation in health and disease, and offer an explanation of why T(H)17 cells specifically present in the intestinal lamina propria.     

Studies on chemotherapy of parasitic helminths (V). Effects of niclosamide on the motility of various parasitic helminths

Summary Niclosamide, a well-known antitapeworm drug, caused spastic and/or paralytic actions on the motility of various preparations including parasitic cestodes, trematodes, nematodes, and host isolated tissues.     

Further evidence for the dissociation of digoxin-like immunoreactivity from Na+,K(+)-ATPase inhibitory activity

The effects of adrenalectomy or nephrectomy, carried out one hour previously, on the levels of endogenous digitalis-like factors were determined in rat plasma. Factors were assayed by digoxin-like immunoreactivity and direct Na+,K(+)-ATPase inhibitory activity. Digoxin-like immunoreactivity significantly decreased one hour after bilateral ablation of adrenals, while Na+,K(+)-ATPase inhibitory activity remained unaltered. There were no changes in either activity one hour after bilateral nephrectomy. These results suggest that digoxin-like immunoreactivity may be derived from the adrenal gland or under adrenal control and the major substances detected by digoxin-like immunoreactivity and direct Na+,K(+)-ATPase inhibitory activity may be different.     

Natural occurrence of trichothecenes (nivalenol,deoxynivalenol, T2) and zearalenone in corn

Summary Samples of corn suspected of causing infertility and refusal symptoms were analyzed and found to contain nivalenol, deoxynivalenol, T₂ toxin and zearalenone, metabolites fromFusarium species.     

Airglow observation by Fabry-Perot interferometer

An all-sky and a scanning Fabry-Perot interferometers (FPI) have been developed for observations of vertical winds and two-dimensional atmospheric motions in the low-thermosphere and the mesosphere region by the measurement of Doppler shift and broadening of airglow emission lines. The system of FPI is described and the method of data analysis is proposed, an example of observation is also given. Ai Yong: born in 1958, Ph.D graduate student     

Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility

Ath1 is a quantitative trait locus on mouse chromosome 1 that renders C57BL/6 mice susceptible and C3H/He mice resistant to diet-induced atherosclerosis. The quantitative trait locus region encompasses 11 known genes, including Tnfsf4 (also called Ox40l or Cd134l), which encodes OX40 ligand. Here we report that mice with targeted mutations of Tnfsf4 had significantly (P 相似文献   

A circumstellar disk associated with a massive protostellar object

The formation process for stars with masses several times that of the Sun is still unclear. The two main theories are mergers of several low-mass young stellar objects, which requires a high stellar density, or mass accretion from circumstellar disks in the same way as low-mass stars are formed, accompanied by outflows during the process of gravitational infall. Although a number of disks have been discovered around low- and intermediate-mass young stellar objects, the presence of disks around massive young stellar objects is still uncertain and the mass of the disk system detected around one such object, M17, is disputed. Here we report near-infrared imaging polarimetry that reveals an outflow/disk system around the Becklin-Neugebauer protostellar object, which has a mass of at least seven solar masses (M(o)). This strongly supports the theory that stars with masses of at least 7M(o) form in the same way as lower mass stars.     

Study on Growth of GdBaSrCu_3O_(7-δ) Single Crystal

1 Results It is generally known that CuO2 planes of layered cuprate superconductors play a major role on the variation of critical temperature,Tc.In order to investigate their microscopic and electronic properties,preparation of such materials in single crystal form with highly structure orientation is very important.Crystal growth techniques for copper oxide materials have greatly improved since the discovery of high Tc superconductor materials[1].However,a strong reaction between CuO flux and crucible material has been a serious problem in crystal growth by using crucible,especially in a self-flux slow cooling method that needs long time.It is important to avoid the contamination from crucible material and also the ‘creeping out' problem of CuO flux during long time and high sintering temperature.In this study,we attempted to grew the GdBaSrCu3O7-δ single crystals via self-flux slow cooling technique.They were grown from CuO-rich nonstoichiometric solutions as similar as the YBCO case with approximately cation and powder ratio used as reported before[2-3].