Inhibition of Membrane-Active Peptides by Fatty Acid–Peptide Hybrids

Nine fatty acid–peptide hybrid molecules were constructed using the general formula CH₃(CH₂) _n CO-Phe Asp Cys-amide and tested for their ability to inhibit cell lysis induced by the membrane-active peptide melittin. All of these molecules, where n = 4–14, inhibited the action of melittin to some extent, but the longer carbon chains were most effective. Several potential inhibitors were also constructed with conservative substitutions in the peptide portion of the molecule. All were effective to varying degrees. We concluded that in the hexapeptide inhibitor published by Blondelle et al. (1993), the role of the first three residues is only to provide hydrophobic interaction with the melittin and has no particular amino acid sequence specificity. Some of these inhibitors were found to inhibit the lytic activity of a melittin analogue which had only superficial sequence similarity to melittin and also a truncated form of melittin, indicating the generality of the action of the inhibitors.Deceased 5/4/98     

Extending the Cellulosome Paradigm: the Modular Clostridium thermocellum Cellulosomal Serpin PinA Is a Broad-Spectrum Inhibitor of Subtilisin-Like Proteases

Clostridium thermocellum encodes a cellulosomal, modular, and thermostable serine protease inhibitor (serpin), PinA. PinA stability but not inhibitory activity is affected by the Fn(III) and Doc(I) domains, and PinA is a broad inhibitor of subtilisin-like proteases and may play a key role in protecting the cellulosome from protease attack.     

Interacting Effects of Discharge and Channel Morphology on Transport of Semibuoyant Fish Eggs in Large,Altered River Systems

Habitat fragmentation and flow regulation are significant factors related to the decline and extinction of freshwater biota. Pelagic-broadcast spawning cyprinids require moving water and some length of unfragmented stream to complete their life cycle. However, it is unknown how discharge and habitat features interact at multiple spatial scales to alter the transport of semi-buoyant fish eggs. Our objective was to assess the relationship between downstream drift of semi-buoyant egg surrogates (gellan beads) and discharge and habitat complexity. We quantified transport time of a known quantity of beads using 2–3 sampling devices at each of seven locations on the North Canadian and Canadian rivers. Transport time was assessed based on median capture time (time at which 50% of beads were captured) and sampling period (time period when 2.5% and 97.5% of beads were captured). Habitat complexity was assessed by calculating width∶depth ratios at each site, and several habitat metrics determined using analyses of aerial photographs. Median time of egg capture was negatively correlated to site discharge. The temporal extent of the sampling period at each site was negatively correlated to both site discharge and habitat-patch dispersion. Our results highlight the role of discharge in driving transport times, but also indicate that higher dispersion of habitat patches relates to increased retention of beads within the river. These results could be used to target restoration activities or prioritize water use to create and maintain habitat complexity within large, fragmented river systems.     

Evolutionary rescue by beneficial mutations in environments that change in space and time

A factor that may limit the ability of many populations to adapt to changing conditions is the rate at which beneficial mutations can become established. We study the probability that mutations become established in changing environments by extending the classic theory for branching processes. When environments change in time, under quite general conditions, the establishment probability is approximately twice the ‘effective selection coefficient’, whose value is an average that gives most weight to a mutant''s fitness in the generations immediately after it appears. When fitness varies along a gradient in a continuous habitat, increased dispersal generally decreases the chance a mutation establishes because mutations move out of areas where they are most adapted. When there is a patch of favourable habitat that moves in time, there is a maximum speed of movement above which mutations cannot become established, regardless of when and where they first appear. This critical speed limit, which is proportional to the mutation''s maximum selective advantage, represents an absolute constraint on the potential of locally adapted mutations to contribute to evolutionary rescue.     

Determination of the relative and absolute stereochemistry of a potent and α1A-selective adrenoceptor antagonist

The binding affinities and selectivities of antagonists Figure 1 and Scheme 2 for the α_1A-adrenoceptor are dependent on the stereochemical orientation of the groups at the C-4 and C-5 positions of the oxazolidinone ring. The unambiguous assignment of the relative and absolute configurations of the diastereomers of SNAP 7915 (Figure 1 and Scheme 2) is reported.