Valerie Vidal | PubMed Health

PubMed2002

A class of potent antimalarials and their specific accumulation in infected erythrocytes.

During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites Plasmodium falciparum and P. vivax and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with P. falciparum and P. cynomolgi.

Animals↗

PubMed2002

Early gonadal development: exploring Wt1 and Sox9 function.

Prior to sex determination the gonadal anlage is formed as a bipotential primordium with the capacity to differentiate into either testes or ovaries depending on the presence or absence of the Sry gene. Knockout experiments have implicated five genes in the formation or survival of the gonadal primordium: Wt1, Sf1, Lim1, Lhx9 and Emx2. We are particularly interested in the Wilms tumour suppressor, WT1, which is characterized by complex posttranscriptional modifications. Here we will focus on published in vitro evidence suggesting distinct functions for the various isoforms and present our own results from in vivo experiments. Our data suggest that WT1 is an important regulator of the transcription or stability of the sex-determining gene Sry. One of the first genes expressed after the initial male sex-determining signal is the Sox9 gene. Human SOX9 has been implicated in male-to-female sex reversal. To analyse Sox9 function in mouse development we have performed transgenic experiments and ectopically expressed this gene in XX gonads. Our data indicate that Sox9 is sufficient to induce testis formation in mice. Here we will discuss our new data and present an updated model for Wt1 and Sox9 function in gonad formation and sex determination.

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