A rapid means of sex identification in Silene latifolia by use of flow cytometry

Sex identification in dioecious plants using nonflowering material would have broad applications in both basic and applied research. We present a method using flow cytometry for diagnosing the sex of the dioecious species Silene latifolia Poiret (Caryophyllaceae) by means of sexual differences in nuclear DNA content and base-pair composition. Males have a significantly larger genome, attributable to the known sex-chromosome heteromorphism. Males and females also differ in the AT/GC composition, attributable to differences in non-recombining portions of the sex chromosomes. The two measures enable assignment of individuals to sex with a combined error rate of 9%. These results for S. latifolia indicate useful directions for future research into sex diagnostics for other dioecious species.</p

Optimization of a Potent Class of Arylamide Colony-Stimulating Factor-1 Receptor Inhibitors Leading to Anti-inflammatory Clinical Candidate 4-Cyano-<i>N</i>-[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1<i>H</i>-imidazole-2-carboxamide (JNJ-28312141)

A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by <b>8</b> and <b>21</b>, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (<b>23</b>, FMS IC₅₀ = 0.69 nM, cell assay IC₅₀ = 2.6 nM). Compound <b>23</b> also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials