Taste, A New Incentive to Switch to (R)-Praziquantel in Schistosomiasis Treatment

Schistosomiasis, or Bilharzia, is a parasitic disease caused by flatworms, which affects about 200 million people worldwide. Praziquantel (PZQ) is the drug compound of choice in the control and treatment of this disease. Only half of the drug dose currently administered actually has activity against schistosomiasis, whereas the other half has no activity. Therefore, the WHO has assigned the low-cost preparation of the pure active component a key priority for future PZQ research and development. PZQ has two major administration drawbacks, the first being the high dose needed, the second its well documented bitter taste. Attempts of masking the unpleasant taste have not been successful. We hypothesized that the non-active component in PZQ would be the main contributor to the unpleasant taste of the drug. We determined the extent of bitterness for regular PZQ compared to the pure active component in a taste study in humans. We found that the pure active component alone is significantly less bitter than regular PZQ. This new finding should serve as an additional incentive for the PZQ research and development community to provide a low-cost, large-scale preparation route to the pure active component of PZQ

DXD Motif-Dependent and -Independent Effects of the Chlamydia trachomatis Cytotoxin CT166

The Gram-negative, intracellular bacterium Chlamydia trachomatis causes acute and chronic urogenital tract infection, potentially leading to infertility and ectopic pregnancy. The only partially characterized cytotoxin CT166 of serovar D exhibits a DXD motif, which is important for the enzymatic activity of many bacterial and mammalian type A glycosyltransferases, leading to the hypothesis that CT166 possess glycosyltransferase activity. CT166-expressing HeLa cells exhibit actin reorganization, including cell rounding, which has been attributed to the inhibition of the Rho-GTPases Rac/Cdc42. Exploiting the glycosylation-sensitive Ras(27H5) antibody, we here show that CT166 induces an epitope change in Ras, resulting in inhibited ERK and PI3K signaling and delayed cell cycle progression. Consistent with the hypothesis that these effects strictly depend on the DXD motif, CT166 with the mutated DXD motif causes neither Ras-ERK inhibition nor delayed cell cycle progression. In contrast, CT166 with the mutated DXD motif is still capable of inhibiting cell migration, suggesting that CT166 with the mutated DXD motif cannot be regarded as inactive in any case. Taken together, CT166 affects various fundamental cellular processes, strongly suggesting its importance for the intracellular survival of chlamydia

Interlaboratory comparison of short-circuit current versus irradiance linearity measurements of photovoltaic devices

This work presents the results of the first interlaboratory comparison of linearity measurements of short-circuit current versus irradiance that includes a wide variety of photovoltaic (PV) device types, from reference cells to full-size modules. The aim of this inter-comparison was to compare the methods employed and to collect new inputs useful for the revision of the standard IEC 60904-10, which deals with linearity measurements for PV devices. The procedures and facilities employed by the partners include the differential spectral responsivity, the white light response, the solar simulator method and the two-lamp method. The facilities are generically described and compared and their main sources of uncertainty are discussed. Comparison results show good agreement within declared uncertainties between all partners. A few minor exceptions under low-light conditions raise questions of possible uncertainty underestimation for these specific conditions. The overall outcome of the comparison also highlights the importance of considering correlations in the uncertainty budget, which can potentially improve the overall stated uncertainty. A critical review is made of the data analysis adopted in the standard IEC 60904-10 to calculate the linearity degree of the short-circuit current towards irradiance. The analysis review suggests a way to make results based on different methods more comparable and less prone to erroneous linearity assessment.JRC.C.2-Energy Efficiency and Renewable