Effects of aphidicolin on Entamoeba histolytica growth and DNA synthesis

We have previously demonstrated that DNA polymerase activity of Entamoeba histolytica is inhibited by aphidicolin, which is a specific inhibitor of eukaryotic nuclear replicative DNA polymerases. The present study was aimed to evaluate the effect of aphidicolin on growth and DNA synthesis by this parasite. Aphidicolin blocked the growth of axenic E. histolytica strain HM-1:IMSS. DNA synthesis was also inhibited by aphidicolin when assayed by incorporation of [3H]thymidine into the DNA. The inhibitory effect of aphidicolin on the growth of E. histolytica was abrogated by removal of the drug, and exposure to 3 microg/ml of the drug for at least 48 hr had little effect on the viability. Synchronous growth was observed in the recovery phase after removal of aphidicolin.     

Combination of the Glutaminyl Cyclase Inhibitor PQ912 (Varoglutamstat) and the Murine Monoclonal Antibody PBD-C06 (m6) Shows Additive Effects on Brain Aβ Pathology in Transgenic Mice

Compelling evidence suggests that pyroglutamate-modified Aβ (pGlu3-Aβ; AβN3pG) peptides play a pivotal role in the development and progression of Alzheimer’s disease (AD). Approaches targeting pGlu3-Aβ by glutaminyl cyclase (QC) inhibition (Varoglutamstat) or monoclonal antibodies (Donanemab) are currently in clinical development. Here, we aimed at an assessment of combination therapy of Varoglutamstat (PQ912) and a pGlu3-Aβ-specific antibody (m6) in transgenic mice. Whereas the single treatments at subtherapeutic doses show moderate (16–41%) but statistically insignificant reduction of Aβ42 and pGlu-Aβ42 in mice brain, the combination of both treatments resulted in significant reductions of Aβ by 45–65%. Evaluation of these data using the Bliss independence model revealed a combination index of ≈1, which is indicative for an additive effect of the compounds. The data are interpreted in terms of different pathways, in which the two drugs act. While PQ912 prevents the formation of pGlu3-Aβ in different compartments, the antibody is able to clear existing pGlu3-Aβ deposits. The results suggest that combination of the small molecule Varoglutamstat and a pE3Aβ-directed monoclonal antibody may allow a reduction of the individual compound doses while maintaining the therapeutic effect.     

Super self-aligned GaAs RF switch IC with 0.25 dB extremely lowinsertion loss for mobile communication systems

An extremely low loss switch IC has been implemented by using a 0.15 μm-gate super self-aligned FET with reduced drain/source area. Both off-state-capacitance and the specific on-resistance of the implemented FET have been dramatically reduced by the novel device structure. The experimentally fabricated switch IC showed the low insertion loss of 0.25 dB at an added power of 35 dBm at a frequency of 0.9 GHz, which is the lowest value ever reported     

A high efficiency GaAs MCM power amplifier for 1.9 GHz digitalcordless telephones

A GaAs MCM power amplifier has been developed for 1.9-GHz digital cordless telephones. Power-added efficiency of 40.2% and P_1dB of 22.2 dBm have been obtained at drain supply voltage of 3.6 V. Adoption of the multilayer MCM structure, i.e., multilayer microwave integrated circuits (MuMIC), and on-chip ferroelectric capacitors successfully reduced the GaAs total chip area to be 1.1 mm². We consider that the MuMIC is the most effective candidate for high frequency circuits