Discovery of a novel series of Notch-sparing gamma-secretase inhibitors

Using a cell-based assay, we have identified a new series of Notch-sparing γ-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved γ-secretase inhibitory potency and Notch-sparing selectivity.     

Genetic population structure of perch Perca fluviatilis along the Swedish coast of the Baltic Sea

In this study, the genetic variation of perch Perca fluviatilis from 18 different sites along the Swedish coast of the Baltic Sea was assessed. There was a relative strong support for isolation by distance and the results suggest an overall departure from panmixia. The level of genetic divergence was moderate (global F(ST) = 0·04) and indications of differences in the population genetic structure between the two major basins (central Baltic Sea and Gulf of Bothnia) in the Baltic Sea were found. There was a higher level of differentiation in the central Baltic Sea compared to the Gulf of Bothnia, and the results suggest that stretches of deep water might act as barriers to gene flow in the species. On the basis of the estimation of genetic patch size, the results corroborate previous mark--recapture studies and suggest that this is a species suitable for local management. In all, the findings of this study emphasize the importance of considering regional differences even when strong isolation by distance characterize the genetic population structure of species.     

Experimental analyses of intra- and intersexual competition in red-winged blackbirds

The roles of intra- and intersexual selection in determiningharem size for many polygynous birds have proved difficult toseparate. We designed experiments to feed only one sex to distinguishbetween intra- and intersexual selection in polygynous red-wingedblackbirds. We then tested whether choices made by females benefitfemales. Our experiments were conducted on a number of differentmarines, so we could evaluate whether females were choosingmales within marshes or whether they are choosing their breedingsituation primarily by making choices between different marshes.Females choosing between marshes strongly preferred marsheswith males that had supplemental food and experimentally increaseddisplay rates. At the marsh level, some male displays were predictorsof larger harem size and of greater nesting success. But whilefemale choice was very strong among marshes, we detected onlyweak female preference for individual male traits within marshes.These results suggest that problems of scale probably affectstudies of mate choice in avian breeding systems in ways that,to the best of our knowledge, have not previously been investigatedby behavioral ecologists     

Thymic nuclear matrix associated activity is not V(D)J recombinase

It was previously reported that nuclear matrix isolated from young rat thymus contained an activity that supported V(D)J recombination at a high efficiency (Dave et al., BIOCHEMISTRY 30: 4763-4767, 1991). A similar type of activity is also detected in the matrix prepared from fetal calf thymus. However, restriction enzyme mapping analyses of the recombined product clearly suggest that the double antibiotic resistance exhibited by the matrix treated plasmid substrate is not a consequence of V(D)J signal sequence recombination.     

Contact Dermatitis in Home Helps Following the Use of Enzyme Detergents

Twelve women in the home help service in Nottingham developed dermatitis after using enzyme detergents. A survey based on a questionary showed an incidence of 5% among those using them. The enzyme appears to act as a primary irritant.