Role of follicular dendritic cells in the early HIV-1 infection: in vitro model without specific antibody

About 90% of HIV-1 RNA in the lymph nodes is reported to localize in follicular dendritic cellsnetwork (FDC-NW) as early as several days after infection and as much as that in the late stage. But the mechanism remains to be fully understood. To elucidate the role of follicular dendritic cells (FDC) in the early stage of HIV-1 infection, FDC-like cell strains (FDCLC) were established and they were characterized in the co-culture system with T cells for their effect on HIV-1 trapping and replication in p24 immunoassay, immunohistochemistry as well as confocal and electronmicroscopy. Established FDCLC were positive for CNA-42, S-100alpha and intercellular desmosome-like junctions. L-SIGN and DC-SIGN were also detected in FDCLC. Alu-HIV-1 PCR analysis showed no HIV-1 integration in FDCLC. FDCLC trapped HIV-1 and transferred them to uninfected MOLT-4 T cells (MOLT-4) efficiently in the absence of specific antibody. FDCLC also accelerated HIV-1 replication in HIV-1-pre-exposed MOLT-4. These unique FDCLC effects were explained, at least partly, by the fact that FDCLC up-regulated CD4 expression in MOLT-4 and helped T cells escape from apoptosis in the co-culture. These data suggest that FDC/FDCLC engage not only in trapping but also in active expansion of HIV-1 in the absence of specific antibody.     

Occurrence of the primary cell wall polysaccharide rhamnogalacturonan II in pteridophytes, lycophytes, and bryophytes. Implications for the evolution of vascular plants

Borate ester cross-linking of the cell wall pectic polysaccharide rhamnogalacturonan II (RG-II) is required for the growth and development of angiosperms and gymnosperms. Here, we report that the amounts of borate cross-linked RG-II present in the sporophyte primary walls of members of the most primitive extant vascular plant groups (Lycopsida, Filicopsida, Equisetopsida, and Psilopsida) are comparable with the amounts of RG-II in the primary walls of angiosperms. By contrast, the gametophyte generation of members of the avascular bryophytes (Bryopsida, Hepaticopsida, and Anthocerotopsida) have primary walls that contain small amounts (approximately 1% of the amounts of RG-II present in angiosperm walls) of an RG-II-like polysaccharide. The glycosyl sequence of RG-II is conserved in vascular plants, but these RG-IIs are not identical because the non-reducing L-rhamnosyl residue present on the aceric acid-containing side chain of RG-II of all previously studied plants is replaced by a 3-O-methyl rhamnosyl residue in the RG-IIs isolated from Lycopodium tristachyum, Ceratopteris thalictroides, Platycerium bifurcatum, and Psilotum nudum. Our data indicate that the amount of RG-II incorporated into the walls of plants increased during the evolution of vascular plants from their bryophyte-like ancestors. Thus, the acquisition of a boron-dependent growth habit may be correlated with the ability of vascular plants to maintain upright growth and to form lignified secondary walls. The conserved structures of pteridophyte, lycophyte, and angiosperm RG-IIs suggests that the genes and proteins responsible for the biosynthesis of this polysaccharide appeared early in land plant evolution and that RG-II has a fundamental role in wall structure.     

Two morphological types of cell appendages on a strongly adhesive bacterium, Acinetobacter sp. strain Tol 5

Two morphological types of appendages, an anchor-like appendage and a peritrichate fibril-type appendage, have been observed on cells of an adhesive bacterium, Acinetobacter sp. strain Tol 5, by use of recently developed electron microscopic techniques. The anchor extends straight to the substratum without branching and tethers the cell body at its end at distances of several hundred nanometers, whereas the peritrichate fibril attaches to the substratum in multiple places, fixing the cell at much shorter distances.     

Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors

In a previous paper, we reported that an imidazole derivative 1 exhibited a potent inhibitory activity of 20-HETE synthase (1; IC(50) value of 5.7 nM), but this compound also exhibited little selectivity for cytochrome P450s (CYPs). We examined some derivatives of imidazole 1 which had an amino group on the side chain, and found that a dimethylaminohexyloxy derivative (3g; IC(50) value of 8.8 nM) showed potent and selective inhibitory activity.     

(+)-3-[2-(Benzo[b]thiophen-2-yl)-2-oxoethyl]-1-azabicyclo[2.2.2]octane as potent agonists for the alpha7 nicotinic acetylcholine receptor

A series of 3-substituted 1-azabicyclo[2.2.2]octanes was discovered as the alpha7 nicotinic acetylcholine (alpha7) receptor agonists. It was found that (+)-3-[2-(benzo[b]thiophen-2-yl)-2-oxoethyl]-1-azabicyclo[2.2.2]octane (+)-15b has potent agonistic activity for the alpha7 receptor.     

Cathepsin L is crucial for a Th1-type immune response during Leishmania major infection

Prior to the activation of CD4+ T cells, exogenous proteins are digested by endo/lysosomal enzymes in antigen-presenting cells (APCs) to produce antigenic peptides that are presented on MHC class II molecules. In the studies described here, the functional significance of cathepsin L for antigen processing and Th1/Th2 differentiation in experimental leishmaniasis was investigated. We first demonstrated that cathepsin L is one of the candidates for endo/lysosomal enzymes in the processing of soluble Leishmania antigen (SLA) by using CLIK148, a specific inhibitor of cathepsin L. Treatment of BALB/c or DBA/2 mice with CLIK148 exacerbated the disease by enhancing an SLA-specific Th2-type response such as IL-4 production. CLIK148 did not exert any direct influence on Leishmania major promastigotes themselves or on the course of L. major infection in SCID mice. Taken together, these findings suggest that treatment of host mice with CLIK148 affects the processing of SLA in APCs, resulting in the potentiation of Th2-type immune responses and thus leading to exacerbation of the disease. Furthermore, endo/lysosomal cathepsin L was found to be functionally distinct from previously described cathepsins B and D.     

The budget of dissolved trace metals in Lake Biwa,Japan

A comprehensive study on the dynamics of dissolved elements (Mg, Al, Si, P, Ca, V, Cr, Mn, Fe, Ni, Zn, As, Sr, Y, W, and U) in Lake Biwa was carried out using a clean technique. Lake water samples (n = 523) were collected from six stations in the North Basin and three stations in the South Basin. River water samples (n = 178) were collected from 14 major rivers flowing into the North Basin. Rainwater samples (n = 89) were collected at Otsu. The river water was enriched with Mn, Al, Fe, P, and Zn and the rainwater was enriched with Zn, Al, Fe, and Mn compared to North Basin water during winter mixing. The residence times of dissolved species were estimated on the basis of input through the rivers and rain. The residence times for Ca, Mg, and Sr were about 8 years, the same as that for water. Mn, Al, Fe, and Zn showed the shortest residence times (0.05–0.19 year). A budget calculation suggested that more than 60% of the input of dissolved Si, P, V, Cr, Mn, Fe, Ni, and Zn was scavenged and retained in the lake sediments and/or discharged as suspended particles.