Telaprevir for Previously Treated Chronic HCV Infection

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

The first catalytic step of the light-driven enzyme protochlorophyllide oxidoreductase proceeds via a charge transfer complex

In chlorophyll biosynthesis protochlorophyllide reductase (POR) catalyzes the light-driven reduction of protochlorophyllide (Pchlide) to chlorophyllide, providing a rare opportunity to trap and characterize catalytic intermediates at low temperatures. Moreover, the presence of a chlorophyll-like molecule allows the use of EPR, electron nuclear double resonance, and Stark spectroscopies, previously used for the analysis of photosynthetic systems, to follow catalytic events in the active site of POR. Different models involving the formation of either radical species or charge transfer complexes have been proposed for the initial photochemical step, which forms a nonfluorescent intermediate absorbing at 696 nm (

Generalising the drift rate distribution for linear ballistic accumulators

The linear ballistic accumulator model is a theory of decision-making that has been used to analyse data from human and animal experiments. It represents decisions as a race between independent evidence accumulators, and has proven successful in a form assuming a normal distribution for accumulation ("drift") rates. However, this assumption has some limitations, including the corollary that some decision times are negative or undefined. We show that various drift rate distributions with strictly positive support can be substituted for the normal distribution without loss of analytic tractability, provided the candidate distribution has a closed-form expression for its mean when truncated to a closed interval. We illustrate the approach by developing three new linear ballistic accumulation variants, in which the normal distribution for drift rates is replaced by either the lognormal, Fréchet, or gamma distribution. We compare some properties of these new variants to the original normal-rate model

Modification of electron transfer from the quinone electron carrier, A(1), of Photosystem 1 in a site directed mutant D576 double right arrow L within the Fe-S(x) binding site of PsaA and in second site suppressors of the mutation in Chlamydomonas reinhardtii

A site directed mutant of the Photosystem I reaction center of Chlamydomonas reinhardtii has been described previously. [Hallahan et al. (1995) Photosynth Res 46: 257–264]. The mutation, PsaA: D576L, changes the conserved aspartate residue adjacent to one of the cysteine ligands binding the Fe-SX center to PsaA. The mutation, which prevents photosynthetic growth, was observed to change the EPR spectrum of the Fe-SA/B centers bound to the PsaC subunit. We suggested that changes in binding of PsaC to the PsaA/PsaB reaction center prevented efficient electron transfer. Second site suppressors of the mutation have now been isolated which have recovered the ability to grow photosynthetically. DNA analysis of four suppressor strains showed the original D576L mutation is intact, and that no mutations are present elsewhere within the Fe-SX binding region of either PsaA or PsaB, nor within PsaC or PsaJ. Subsequent genetic analysis has indicated that the suppressor mutation(s) is nuclear encoded. The suppressors retain the altered binding of PsaC, indicating that this change is not the cause of failure to grow photosynthetically. Further analysis showed that the rate of electron transfer from the quinone electron carrier A1 to Fe-SX is slowed in the mutant (by a factor of approximately two) and restored to wild type rates in the suppressors. ENDOR spectra of A1·– in wild-type and mutant preparations are identical, indicating that the electronic structure of the phyllosemiquinone is not changed. The results suggest that the quinone to Fe-SX center electron transfer is sensitive to the structure of the iron-sulfur center, and may be a critical step in the energy conversion process. They also indicate that the structure of the reaction center may be modified as a result of changes in proteins outside the core of the reaction center

Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B

10.1056/NEJMoa021812New England Journal of Medicine3489800-807NEJM