Ovarian failure leading to infertility can be caused by improper prenatal development of the fetal gonad or disruption of the complex postnatal process of folliculogenesis due to alterations in intragonadal or extragonadal regulation. It is critical to have physiological models that mimic events occurring during human development to understand, treat, and prevent ovarian failure in women. Many workers have chosen the mouse as the mammalian model with which to study ovarian function. This review summarizes several key events in female gonadogenesis and folliculogenesis in mice with specific emphasis on spontaneous or induced mutations yielding mouse models that have female infertility owing to ovarian failure. 184 J. A. Elvin and M. M. Matzuk Cohen P, Zhu L and Pollard J (1997) Absence of colony stimulating factor-1 in osteopetrotic (csfm op /csfm op) mice disrupts estrous cycles and ovulation Biology of Reproduction 56 110-118 *Colledge W, Carlton M, Udy G and Evans M (1994) Disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs Nature 370 65-68 Coulombre J and Russell E (1954) Analysis of the pleiotropism at the W-locus in the mouse: the effects of W and W v substitution upon postnatal development of germ cells Journal of Experimental Zoology 126 277-296 Couse J, Curtis S, Washburn T, Lindzey J, Golding T, Lubahn D, Smithies O and Korach K (1995) Analysis of transcription and oestrogen insensitivity in the female mouse after targeted disruption of the oestro-gen receptor gene Molecular Endocrinology 9 1441-1454 Dinchuk J, Car B, Focht R, Johnston J, Jaffee B, Covington M, Contel N, Eng V, Collins R, Czerniak P, Gorry S and Trzaskos J (1995) Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II Nature 378 406-409 *Dong J, Albertini D, Nishimori K, Kumar T, Lu N and Matzuk M (1996) Growth differentiation factor-9 is required during early ovarian folliculo-genesis Nature 383 531-535

Recommendations about structuring proteomic biomarker studies should increase the probability that such markers will be clinically useful.

Vitamin traffic, the production of organic growth factors by some microbial community members and their use by other taxa, is being scrutinized as a potential explanation for the variation and highly connected behavior observed in ocean plankton by community network analysis. Thiamin (vitamin B1), a cofactor in many essential biochemical reactions that modify carbon–carbon bonds of organic compounds, is distributed in complex patterns at subpicomolar concentrations in the marine surface layer (0–300 m). Sequenced genomes from organisms belonging to the abundant and ubiquitous SAR11 clade of marine chemoheterotrophic bacteria contain genes coding for a complete thiamin biosynthetic pathway, except for thiC, encoding the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) synthase, which is required for de novo synthesis of thiamin’s pyrimidine moiety. Here we demonstrate that the SAR11 isolate ‘Candidatus Pelagibacter ubique’, strain HTCC1062, is auxotrophic for the thiamin precursor HMP, and cannot use exogenous thiamin for growth. In culture, strain HTCC1062 required 0.7 zeptomoles per cell (ca. 400 HMP molecules per cell). Measurements of dissolved HMP in the Sargasso Sea surface layer showed that HMP ranged from undetectable (detection limit: 2.4 pm) to 35.7 pm, with maximum concentrations coincident with the deep chlorophyll maximum. In culture, some marine cyanobacteria, microalgae and bacteria exuded HMP, and in the Western Sargasso Sea, HMP profiles changed between the morning and evening, suggesting a dynamic biological flux from producers to consumers.

No abstract

Escherichia coli uracil-DNA glycosylase was shown to catalyze the hydrolysis of a site-specific uracil residue from a defined single-stranded oligonucleotide (25-mer). With duplex 25-mer, the rate of uracil removal from double-stranded DNA containing a U.G mispair was approximately 2-fold greater than a U.A base pair. The mechanism by which E. coli and rat liver mitochondrial uracil-DNA glycosylase located sequential uracil residues within double-stranded DNA was investigated. Two concatemeric polynucleotide substrates were constructed by ligation of homologous 5'-end 32P-labeled 25-mer double-stranded oligonucleotides that contained either a site-specific U.G or U.A target site at intervals of 25 nucleotides along one strand of the DNA. Reaction of uracil-DNA glycosylase with these concatemeric DNAs, followed by alkaline hydrolysis of the resultant AP-sites, would produce predominantly [32P]25-mer products, if a processive mechanism was used to locate successive uracil residues, or oligomeric multiples of [32P]25-mer, if a distributive mode was exhibited. Both the bacterial and the mitochondrial enzymes were found to act processively on U.A- and U.G-containing DNA in the absence of NaCl, based on the initial rate of 25-mer produced relative to the total amount of uracil excised. Approximately 50% of the total uracil excised resulted in the release of 25-mer product. The addition of NaCl (> or = 50 mM) caused reduced processivity on both U.A- and U.G-containing DNA substrates. The mode of action of uracil-DNA glycosylase was very similar to that observed for the EcoRI endonuclease cleavage of restriction sites contained in the same DNA substrate which was used as a positive control.