Totipotent germline blastomeres in Caenorhabditis elegans contain, but do not respond to, factors that promote somatic differentiation in other embryonic cells. Mutations in the maternal gene pie-1 result in the germline blastomeres adopting somatic cell fates. Here we show that pie-1 encodes a nuclear protein, PIE-1, that is localized to the germline blastomeres throughout early development. During division of each germline blastomere, PIE-1 initially associates with both centrosomes of the mitotic spindle. However, PIE-1 rapidly disappears from the centrosome destined for the somatic daughter, and persists in the centrosome of the daughter that becomes the next germline blastomere. The PIE-1 protein contains potential zinc-finger motifs also found in the mammalian growth-factor response protein TIS-11/NUP475 (refs 4-7). The localization and genetic properties of pie-1 provide an example of a repressor-based mechanism for preserving pluripotency within a stem cell lineage.
The empty supine stress test is easy to perform, inexpensive, and without significant risk. By itself, a positive empty supine stress test is essentially diagnostic for genuine stress incontinence, and in combination with a fixed urethra, it is diagnostic for intrinsic urethral sphincter dysfunction. In low-prevalence populations, a negative test reliably excludes the presence of intrinsic urethral sphincter dysfunction. However, for high-prevalence and referral populations, the low predictive values of the test limit its usefulness.
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