At the midblastula transition, the Xenopus laevis embryonic cell cycle is remodeled from rapid alternations between S and M phases to become the complex adult cell cycle. Cell cycle remodeling occurs after zygotic transcription initiates and is accompanied by terminal downregulation of maternal cyclins A1 and B2. We report here that the disappearance of both cyclin A1 and B2 proteins is preceded by the rapid deadenylation of their mRNAs. A specific mechanism triggers this deadenylation. This mechanism depends upon discrete regions of the 3 untranslated regions and requires zygotic transcription. Together, these results strongly suggest that zygote-dependent deadenylation of cyclin A1 and cyclin B2 mRNAs is responsible for the downregulation of these proteins. These studies also raise the possibility that zygotic control of maternal cyclins plays a role in establishing the adult cell cycle.In Xenopus laevis, the first 12 cell cycles following fertilization occur in the absence of transcription. Maternal mRNAs and proteins that are synthesized and stored in the growing oocyte control these early embryonic cell divisions. Zygotic transcription begins upon completion of the 12th cell cycle and, in Xenopus, is referred to as the midblastula transition (MBT) (25). Prior to the MBT, gene expression is controlled by posttranscriptional mechanisms including regulation of the adenylation state of maternal mRNAs. Polyadenylated mRNAs are recruited into polysomes and translated, while deadenylated mRNAs are released from polysomes and translationally silenced (27).In Xenopus, adenylation control regulates both progression through meiosis (oocyte maturation) and the transition from the meiotic to the mitotic cell cycle by regulating levels of cell cycle proteins, including cyclins. The mRNAs encoding cyclins A1, B1, B2, and E1 are synthesized during oogenesis and stored untranslated as poly(A) Ϫ mRNAs until oocyte maturation (5, 35). In response to progesterone, cytoplasmic polyadenylation elements (CPEs) in the 3Ј untranslated region (UTR) trigger polyadenylation and translational activation of these mRNAs, allowing accumulation of cyclin protein and progression through meiosis. After fertilization, cyclin mRNAs are further adenylated and continuously translated (35). However, periodic degradation of cyclin A1, B1, and B2 proteins during each cell cycle allows progression through the first 12 cell divisions (18).The 12th cell division is completed approximately 6 h postfertilization (p.f.) and is followed by remodeling of the cell cycle between cell cycles 13 and 15 (24). The cell cycle is remodeled from a rapid alternation between DNA synthesis and mitosis to become a cell cycle containing gap phases and checkpoint controls. The mechanism of cell cycle remodeling is not well understood, but it is accompanied by temporally specific degradation of maternal cyclin A1, B2, and E1 proteins (14, 33). We define this event as the terminal disappearance of the maternal cyclin protein.Because cyclins A1 and B2 are normally degraded ...

In order to investigate the development of luminance and chromatic temporal contrast sensitivity functions (tCSFs), we obtained chromatic and luminance contrast thresholds from individual 3- and 4-month old infants, and compared them to previously obtained functions in adults. Stimuli were moving sinusoidal gratings of 0.27 cyc/deg, presented at one of five temporal frequencies: 1.0, 2.1, 4.2, 9.4 or 19 Hz (corresponding speeds: 3.8, 7.7, 15, 34, 69 deg/s). Previous studies, including our own, have shown that adult tCSFs are bandpass for luminance stimuli (peaking at 5-10 Hz), yet lowpass for chromatic stimuli (sensitivity falling at > 2 Hz), and that the two functions cross one another near 4-5 Hz when plotted in terms of cone contrast. In the present study, we find that the shapes and peaks of the luminance tCSF in both 3- and 4-months-olds appear quite similar to those of adults. By contrast, chromatic tCSFs in infants are markedly different from those of adults. In agreement with our earlier report (Dobkins, K. R., Lia, B., & Teller, D. Y. (1997). Vision Research, 37(19), 2699-2716), the chromatic function in 3-month-olds is rather flat, lacking the sharp high temporal frequency fall-off characteristic of the adult function. In addition, the luminance tCSF in 3-month-olds is elevated above the chromatic tCSF, and the two functions do not exhibit an adult-like cross-over within the range of temporal frequencies tested. By 4 months of age, substantial development of chromatic contrast sensitivity takes place at the lowest temporal frequencies. Although still immature, the 4-month-old chromatic tCSF has begun to adopt a more adult-like shape. In addition, similar to adults, luminance and chromatic tCSFs in 4-month-olds cross one another near 5 Hz. In adults, magnocellular (M) and parvocellular (P) pathways are thought to underlie the bandpass luminance and lowpass chromatic tCSF, respectively (e.g. Lee, B. B., Pokorny, J., Smith, V. C., Martin, P. R., & Valberg, A. (1990). Journal of the Optical Society of America (a), 7(12), 2223-2236). Based on this correspondence between psychophysical and neural responses in adults, our results suggest that the relatively slow development of the chromatic tCSF in infants may reflect immature chromatic responses in the P pathway and/or reliance on chromatic responses originating in the M pathway.

A large body of evidence has indicated that microglia are the predominant cellular location for HIV-1 in the brains of HIV-1-infected individuals and play a direct role in the development of HIV-1-associated dementia (HAD). Therefore, investigation of the mechanism by which HIV-1-infected microglia contribute to the development of HIV-associated dementia should be facilitated by the creation of a mouse model wherein microglia carry replication-competent HIV-1. To circumvent the inability of HIV-1 to infect mouse cells, we developed a mouse line that is transgenic for a full-length proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1(JR-CSF) (JR-CSF mice), whose T cells and monocytes produce infectious HIV-1. We detected expression of the long terminal repeat-regulated proviral transgene in the microglia of these transgenic mice and demonstrated that it was increased by in vitro and in vivo stimulation with lipopolysaccharide. Furthermore, microglia isolated from JR-CSF mouse brains produced HIV-1 that was infectious in vitro and in vivo. We examined the effect that carriage of the HIV-1 provirus had on chemokine gene regulation in the brains of these mice and demonstrated that MCP-1 gene expression by JR-CSF mouse microglia and brains was more responsive to in vitro and in vivo stimulation with lipopolysaccharide than were microglia and brains from control mice. Thus, this study indicates that the JR-CSF mice may represent a new mouse model to study the effect of HIV-1 replication on microglia function and its contribution to HIV-1-associated neurological disease.

In order to investigate the development of color mechanisms in infants we fitted elliptical detection contours to psychophysically-derived contrast thresholds plotted in L- and M-cone contrast space. Detection ellipses were obtained for 47 infants (ages 2-5 months of age), and were compared to those of six adults tested under nearly identical conditions. The parameters of the fitted ellipses allowed us to address several aspects of color development. First, the lengths and widths were used to assess the relative development of chromatic, with respect to luminance, sensitivity. The results of these analyses revealed a sharp increase in chromatic sensitivity between 3 and 4 months of age, suggesting an accelerated development of chromatic mechanisms around this time. Second, the angles of the ellipses provided estimates of individual red/green isoluminance points. In line with previous reports, we found that isoluminance points do not vary significantly with age. Finally, our ellipse-fitting procedures were used to assess whether color sensitivity is best described by a model that assumes independence between post-receptoral chromatic and luminance mechanisms. Similar to previous results of Kelly and Chang [Kelly, J. P. & Chang, S. (2000). Vision Research 40, 1887-1906] obtained using steady-state visually evoked potentials, only a proportion (approximately half) of our infants exhibited detection contours that were consistent with independent mechanisms, a finding that most likely results from statistical noise in the infant data sets.

The responses of motion mechanisms depend not only on the direction of a stimulus, but also on its contrast, coherence and speed. We examined how contrast, coherence and directional selectivity interact by measuring directional tuning psychophysically across a wide range of coherence and contrast levels. We fit data with a simple model that estimated directional tuning bandwidth using contrast and coherence gain parameters that were based on neurophysiological estimates. This model estimated a bandwidth of approximately 90 degrees for directionally selective mechanisms. Bandwidth was invariant across a wide range of contrasts and coherences, as predicted by models of contrast normalization.