8-Biarylchromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK)

The synthesis and biological evaluation of libraries of 8-biarylchromen-4-ones enabled the elucidation of structure–activity relationships for inhibition of the DNA-dependent protein kinase (DNA-PK), with 8-(3-(thiophen-2-yl)phenyl)chromen-4-one and 8-(3-(thiophen-3-yl)phenyl)chromen-4-one being especially potent inhibitors.     

Development of polymorphic microsatellite markers in sesame (Sesamum indicum L.)

Fifty microsatellite sequences (SSRs) were isolated from an enriched library of sesame (Sesamum indicum L.) using a modified protocol. After screening, 10 polymorphic microsatellites were used to determine their usefulness in diversity analysis among 16 sesame accessions. The number of alleles ranged from three to six alleles per locus with an average of 4.6 alleles. The fragment size varied from 150 bp to 307 bp. Expected heterozygosites (H_E) and polymorphism information contents (PICs) ranged from 0.437 to 0.858 and 0.34 to 0.80, respectively, which indicates the highly informative nature of the microsatellites reported here. These microsatellite markers will be very useful in diversity analysis among a large germplasm collection of sesame present in our Korean gene bank and also in the establishment of its core collection.     

Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries

A solution-phase multiple-parallel synthesis approach was employed for the preparation of 6-, 7- and 8-aryl-substituted chromenone libraries, which were screened as inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). These studies resulted in the identification of 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) as a highly potent and selective DNA-PK inhibitor (IC₅₀ = 14 nM), exhibiting ATP-competitive inhibition kinetics.     

Supporting irrational suicide

In this essay, we present three case studies which suggest that sometimes we are better off supporting a so–called irrational suicide, and that emotional or psychological distress – even if medically controllable – might justify a suicide. We underscore how complicated these decisions are and how murky a physician's moral role can be. We advocate a more individualized route to end–of–life care, eschewing well–meaning, principled, generalizations in favor of a highly contextualized, patient–centered, approach. We conclude that our Western traditions of promoting reasoned behavior and life themselves may at times be counter–productive.     

Feeling of Pleasure to High-Intensity Interval Exercise Is Dependent of the Number of Work Bouts and Physical Activity Status

ObjectivesTo examine the affective responses during a single bout of a low-volume HIIE in active and insufficiently active men.ResultsThere were similar positive affective responses to the first three work bouts between insufficiently active and active men (p > 0.05). However, insufficiently active group displayed lower affective responses over time (work bout 4 to 10) than the active group (p < 0.01). Also, the insufficiently active group displayed lower values of mean, lowest, and highest affective response, as well as lower values of affective response at the highest RPE than the active group (p < 0.001). There were no differences in the RPE and HR between the groups (p > 0.05).ConclusionsInsufficiently active and active men report feelings of pleasure to few work bouts (i.e., 3–4) during low-volume HIIE, while the affective responses become more unpleasant over time for insufficiently active subjects. Investigations on the effects of low-volume HIIE protocols including a fewer number of work bouts on health status and fitness of less active subjects would be interesting, especially in the first training weeks.     

Characterization of Dimorphism in Cladosporium werneckii

Yeast forms of the dimorphic fungus Cladosporium werneckii grow by polar budding and yield a homogeneous yeast phase when cultured at 21 C in an agitated sucrose-salts medium (Czapek-Dox broth). Yeast extract enrichment of such a yeast phase consisting of 10⁴ yeasts per ml induces a quantitative conversion of the yeasts to true hyphae. This conversion is not mediated by a transition cell and is often attended by capsule formation. When 10⁵ or 10⁶ yeasts per ml receive enrichment, a nonquantitative conversion to moniliform hyphae is effected and no capsule formation is observed. Rapid agitation compared to slow agitation or stationary incubation of the nutritionally mediated conversion cultures greatly accelerates the production of lateral hyphal buds or their yeast progenies. These cells appear incapable of undergoing nutritional conversion to hyphae, but instead must grow for several generations in the unenriched sucrose-salts medium to restore conversion competence. Temperature shifts affect directly the morphology and morphogenesis of the yeast in unenriched medium; at 17 C yeasts are smaller and more ovoid than at 21 C, and at 30 C marked conversion of yeasts to moniliform hyphae occurs. A methodology employing the Coulter counter and Coulter channelizer provides evidence that direct correlations do not always exist between the optimum conditions for the growth of C. werneckii and the optimum conditions for its yeast-to-mold conversion.     

Morphology and Infraciliature of Three Species of Eutintinnus (Ciliophora; Tintinnina) with Guidelines for Interpreting Protargol-Stained Tintinnine Ciliates

ABSTRACT. The infraciliatures of three Chesapeake Bay species of Eutintinnus conforming in lorica morphology to E. angustatus, E. pectinis , and E. tenuis were compared following Protargol silver impregnation. The kinetome of these species had a number of shared attributes including: 1) a right and left field that were of similar length and kinetal spacing; 2) two, rarely three, long dorsal kineties composed of monokinetids; 3) a ventral kinety; and 4) the absence of a true posterior kinety. Nonetheless, the specific organization of infraciliary components varied considerably among species. For example, the organization of the ventral kinety and several kineties along the border of the left field was different in all three species. In addition, the dorsal kineties of E. angustatus differed positionally from those of E. pectinis and E. tenuis . Some divergence in oral infraciliature was also noted, with the arrangement of infundibular oral polykinetids in E. pectinis and E. tenuis being distinct from that of E. angustatus . The amount of variation in the infraciliature of Eutintinnus spp. was much greater than previously noted for congeneric species of tintinnines and supports the separation E. angustatus, E. pectinis , and E. tenuis at the generic or subgeneric level.