74 research outputs found
Ivermectin, an unconventional agonist of the glycine receptor chloride channel
The effects of the antihelmintic, ivermectin, were investigated in recombinantly expressed human alpha (1) homomeric and alpha (1)beta heteromeric glycine receptors (GlyRs), At low (0.03 muM) concentrations ivermectin potentiated the response to sub-saturating glycine concentrations, and at higher (greater than or equal to0.03 muM) concentrations it irreversibly activated both alpha (1) homomeric and alpha (1)beta heteromeric GlyRs. Relative to glycine-gated currents, ivermectin-gated currents exhibited a dramatically reduced sensitivity to inhibition by strychnine, picrotoxin, and zinc. The insensitivity to strychnine could not be explained by ivermectin preventing the access of strychnine to its binding site. Furthermore, the elimination of a known glycine- and strychnine-binding site by site-directed mutagenesis had little effect on ivermectin sensitivity, demonstrating that the ivermectin- and glycine-binding sites were not identical. Ivermectin strongly and irreversibly activated a fast-desensitizing mutant GlyR after it had been completely desensitized by a saturating concentration of glycine. Finally, a mutation known to impair dramatically the glycine signal transduction mechanism had little effect on the apparent affinity or efficacy of ivermectin, Together, these findings indicate that ivermectin activates the GlyR by a novel mechanism
Polystyrene-block-poly (methoxy diethylene glycol acrylate)-block-polystyrene triblock copolymers in aqueous solution—a SANS study of the temperature-induced switching behavior
A concentrated solution of a symmetric triblock copolymer with a thermoresponsive poly(methoxy diethylene glycol acrylate) (PMDEGA) middle block and short hydrophobic, fully deuterated polystyrene end blocks is investigated in D2O where it undergoes a lower critical solution temperature-type phase transition at ca. 36 °C. Small-angle neutron scattering (SANS) in a wide temperature range (15–50 °C) is used to characterize the size and inner structure of the micelles as well as the correlation between the micelles and the formation of aggregates by the micelles above the cloud point (CP). A model featuring spherical core-shell micelles, which are correlated by a hard-sphere potential or a sticky hard-sphere potential together with a Guinier form factor describing aggregates formed by the micelles above the CP, fits the SANS curves well in the entire temperature range. The thickness of the thermoresponsive micellar PMDEGA shell as well as the hard-sphere radius increase slightly already below the cloud point. Whereas the thickness of the thermoresponsive micellar shell hardly shrinks when heating through the CP and up to 50 °C, the hard-sphere radius decreases within 3.5 K at the CP. The volume fraction decreases already significantly below the CP, which may be at the origin of the previously observed gel–sol transition far below the CP (Miasnikova et al., Langmuir 28: 4479–4490, 2012). Above the CP, small, and at higher temperatures, large aggregates are formed by the micelles
A Transcription Inhibitor, Actinomycin D, Enhances HIV-1 Replication Through an Interleukin-6-Dependent Pathway
We previously demonstrated that Actinomycin D (ActD) enhanced HIV-1 replication in the MT-2 cell, a human T-cell leukemia virus type-1-infected cell line. The MT-2 cell is known to produce multiple cytokines spontaneously. In this study, we investigated the impact of ActD on the cytokine production from MT-2 cells and HIV-1 replication in a latently infected cell line, U1. MT-2 cells were pulse-treated with 0 or 200 nM of ActD, and culture supernatants were collected 3 days after incubation. Supernatants from untreated cells (Sup0) induced HIV-1 replication by 150-fold in U1 cells. Culture supernatants from ActD-treated cells (Sup200) enhanced HIV-1 replication by 1200-fold. A combination of a sequential chromatographic approach and mass spectrometric analysis identified that the HIV-inducing factors in Sup200 were interleukin (IL)-6 and tumor necrosis factor (TNF)-beta. Quantitative analysis revealed that ActD treatment increased the concentration of IL-6 in Sup200 by 600% compared with that in Sup0 but decreased the amount of TNFbeta in Sup200 by 85%. Northern blot analysis showed that ActD treatment increased IL-6 transcripts; however, no change was seen in TNFbeta transcripts. These results suggest that ActD induces replication of HIV-1 through modulation of cytokine production
Catalpa ovata G. Don
原著和名: キササゲ科名: ノウゼンカズラ科 = Bignoniaceae採集地: 千葉県 千葉市 千葉大学 (下総 千葉市 千葉大学)採集日: 1958/8/1採集者: 萩庭丈壽整理番号: JH026902国立科学博物館整理番号: TNS-VS-97690
Stimuli-Responsive Amphiphilic Polyelectrolyte Heptablock Copolymer Physical Hydrogels: An Unusual pH-Response
An amphiphilic cationic polyelectrolyte based on poly[2-(dimethylamino)ethyl methacrylate] (polyDMA) and poly(n-butyl methacrylate) (polyBuMA) with a BuMA–DMA–BuMA–DMA–BuMA–DMA–BuMA heptablock copolymer architecture was studied in aqueous media. This copolymer was found to form a physical hydrogel via the intermolecular hydrophobic association (physical cross-linking) of the BuMA blocks. The rheological properties of the heptablock hydrogels were investigated as a function of copolymer concentration, and pH. The results showed a peculiar pH-dependence of the rheological properties, remarkably different from those observed with associative telechelic polyelectrolytes. Aqueous solutions of this copolymer were free-flowing sols at low pH (below 2) and high pH (above 8), whereas they turned into gels at intermediate pH values. The rheological properties studied as a function of pH showed two additional stiff–soft–stiff gel transitions at pH 4.5 and 6.5. Small-angle neutron scattering revealed the formation of a 3D transient network of bridged flower-like micelles whose structural characteristics, i.e., micellar radius, hard-sphere radius and hard-sphere volume fraction, were smoothly evolving with the pD
Additional file 1: Figure S1. of Alpha-1-antitrypsin interacts with gp41 to block HIV-1 entry into CD4+ T lymphocytes
Purity and quality of AAT, ΔAAT and C. ΔAAT was prepared following the protocol in Materials and. Next, AAT, purified ΔAAT and C were analyzed on 4–20 % Tris-Glycin SDS-PAGE gel and analyzed by in-gel digestion mass fingerprinting assay (A). Aligned sequences were also shown for AAT, ΔAAT and C (B). (TIF 6959 kb
- …