A theoretical entropy score as a single value to express inhibitor selectivity

Background  

Designing maximally selective ligands that act on individual targets is the dominant paradigm in drug discovery. Poor selectivity can underlie toxicity and side effects in the clinic, and for this reason compound selectivity is increasingly monitored from very early on in the drug discovery process. To make sense of large amounts of profiling data, and to determine when a compound is sufficiently selective, there is a need for a proper quantitative measure of selectivity.     

Late Devonian benthic marine communities of the central Appalachian Allegheny Front

Four benthic marine communities occur in the clastic facies of the prograding Upper Frasnian-Lower Famennian (Upper Devonian) Foreknobs Formation in the Central Appalachians along the Allegheny Front in Maryland, West Virginia, and Virginia. Deep-water, rapidly prograding environments were inhabited by the Ambocoelia-Chonetes Community, dominated by an epifauna of unattached brachiopods. Offshore bar environments were inhabited by the Cyrtospirifer-Camarotoechia Community, exhibiting adaptations to shallow-water, high-energy conditions and probably lowered salinities. Shallow-water, sublittoral environments were inhabited by the Atrypa-Cypricardella Community, a community in which existed a variety of life habitats and a diverse epifaunal and infaunal association of brachiopods and bivalve molluscs. The Leptodesma-Tylothyris Community flourished in nearshore bar-protected environments in the southern region of the study area, whereas in the north the Cyrtospirifer-Camarotoechia Community inhabited nearshore environments in conjunction with the onshore development of a large fluviodeltaic system.     

Historical and Life History Factors in the Biogeography of Mayflies

SYNOPSIS. Cladistic analysis of mayflies suggests that dispersalwas very asymmetrical after the new land connection betweenNorth and South America. Twenty-one genera apparently movedfrom South to North and Central America, but there is good evidencefor only one North American genus moving into the south. Testablepredictions are possible once the boreal (Laurasian) or austral(Gondwanian) designations are made. For example, Paracloeodes,a genus of austral origin, was predicted to be found in SouthAmerica, and in North America in warm rivers north and eastof its known distribution. These predictions have been confirmed.Other characteristics of tropical mayflies, such as length oflarval period and emergence and mating patterns, may be usedto predict habitats and characteristics of present North Americangenera. Merger events and consequent dispersal of organismshave profound influences on distributional patterns, and fromsuch information, biologically useful generalities can be made.     

Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo

Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 and H3K4 methylation from a proximal as well as a more distal site, but only if in a correct orientation. This plasticity indicates that the exact location of the attachment site, the native ubiquitin-lysine linkage and ubiquitination cycles are not critical for trans-histone crosstalk in vivo. The flexibility in crosstalk also indicates that other ubiquitination events may promote H3 methylation.     

The Spontaneous Formation of Antheridia in Onoclea is not Blocked by Light

Onoclea sensibilis gametophytes were grown from spores on ashedsoil and agar to determine if the spontaneous formation of antheridiacan be blocked by light. Under most conditions, dark-grown gametophytesformed antheridia later than or at the same time as gametophytesgrown in the light. Under no circumstances was there a rapidonset of maleness in the dark. These results contradict thehypothesis that, in Onoclea, antheridiogen is required to inducemaleness because light inhibits the formation of antheridia.In the light, antheridia formed on heart-shaped thalli. In darkness,antheridia formed on filamentous gametophytes. The timing ofonset of maleness was affected by temperature and the presenceof sucrose. The effect of sucrose on the comparison betweenlight and dark treatments depended on both substrate and temperature Onoclea sensibilis, L., sensitive fern, fern gametophytes, sexuality, light-induced block     

A METHOD FOR ISOLATION OF CAMPYLOBACTER SPP. (JEJUNI, COLI AND LARI) FROM SHELLFISH AND THE MARINE ENVIRONMENT

A method has been developed to detect thermophilic species of Campylobacter in shellfish, marine and tributary waters, sediment and farm runoff by-products such as manure and silage. The method consists of a 48 h enrichment incubation and subcultured to selective agars. Presumptive colonies confirmed with a latex agglutination (antibodies) to common flagellar antigens of C. jejuni, C. coli and C. lardi. Over an 8 year period, West Coast estuaries (Washington, Oregon, and California) were sampled, resulting in analysis of a total of 512 samples. Results suggest that Campylobacter spp. are well distributed in the marine environment. Two enrichment broths were compared for the recovery of campylobacters from environmental samples. The method described in the Food and Drug Administration Bacteriological Analytical Manual (FDA/BAM) (1984), was compared to a modified method. Use of the modified method described here resulted in higher recovery rates of Campylobacter spp. Recoveries of campylobacters from sediment, shellfish, and water were 10,13, and 28% higher for the modified method, respectively.     

Replication slippage may cause parallel evolution in the secondary structures of mitochondrial transfer RNAs

Presence of the dihydrouridine (D) stem in the mitochondrial cysteine tRNA is unusually variable among lepidosaurian reptiles. Phylogenetic and comparative analyses of cysteine tRNA gene sequences identify eight parallel losses of the D-stem, resulting in D-arm replacement loops. Sampling within the monophyletic Acrodonta provides no evidence for reversal. Slipped-strand mispairing of noncontiguous repeated sequences during replication or direct replication slippage can explain repeats observed within cysteine tRNAs that contain a D-arm replacement loop. These two mechanisms involving replication slippage can account for the loss of the cysteine tRNA D-stem in several lepidosaurian lineages, and may represent general mechanisms by which the secondary structures of mitochondrial tRNAs are altered.