基因差异与不同药物反应

同种药物治疗同种疾病，不同的病人有不同的结果。很快，医生要先为病人做基国检测后再开处方。饱经折磨之后，一位深陷苦恼的年轻妇女拖着疲惫的身躯求助于医生。医生诊断为严重抑郁症后，安慰她道：“现在，我们能给你做个DNA检测，看看什么药对你最恰当。”他从她头上拔下一根头发，“等下午报告出来后我再开处方，你的病很快就会好。”她首次露出长久不见的充满希望的笑容。类似的情景，可能不要很久就会出现。从制药公司和生物技术公司看来，病人不久就能用上适合其本人基因组成的药品。今天的医生只会让这位年轻妇女去试用一种药品…     

The C4-dicarboxylate transport system ofRhizobium meliloti and its role in nitrogen fixation during symbiosis with alfalfa (Medicago sativa)

TheRhizobium meliloti C₄-dicarboxylate transport (Dct) system is essential for an effective symbiosis with alfalfa plants. C₄-dicarboxylates are the major carbon source taken up by bacteroids. Genetic analysis of Dct^– mutant strains led to the isolation of thedct carrier genedctA and the regulatory genesdctB anddctD. The carrier genedctA is regulated in free-living cells by the alternative sigma factor RpoN and the two-component regulatory system DctB/D. In addition, DctA is involved in its own regulation, possibly by interacting with DctB. In bacteroids, besides the DctB/DctD system an additional symbiotic activator is thought to be involved indctA expression. Further regulation ofdctA in the free-living state is reflected by diauxic growth of rhizobia, with succinate being the preferred carbon source. The tight coupling of C₄-dicarboxylate transport and nitrogen fixation is revealed by a reduced level of C₄-dicarboxylate transport in nitrogenase negative bacteroids.     

On the excretion of 17-ketosteroids in guinea pigs

Zusammenfassung Im Harn von weiblichen Meerschweinchen wurde im Gegensatz zu männlichen Tieren Epiandrosteron als Haupt-17-Ketosteroid nachgewiesen.Untersuchungen über die 17-Ketosteroidkonjugate im Harn von weiblichen Meerschweinchen ergaben, dass ein grosser Teil (30–40%) als freie Steroide nachweisbar ist. 40–50% liegen als Schwefelsäurekonjugate und 3–6% wahrscheinlich als Glucuronide vor. Bei den konjugierten 17-Ketosteroiden handelt es sich vornehmlich um 11-oxygenierte Steroide.     

The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours

In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males. In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells, and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine to uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.