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FOXO transcription factors have been shown to regulate longevity in model organisms and are associated with longevity in humans. To gain insight into how FOXO functions to increase lifespan, we examined the subcellular localization of DAF-16 in C. elegans. We show that DAF-16 is localized to endosomes and that this endosomal localization is increased by the insulin-IGF signaling (IIS) pathway. Endosomal localization of DAF-16 is modulated by endosomal trafficking proteins. Disruption of the Rab GTPase activating protein TBC-2 increases endosomal localization of DAF-16, while inhibition of TBC-2 targets, RAB-5 or RAB-7 GTPases, decreases endosomal localization of DAF-16. Importantly, the amount of DAF-16 that is localized to endosomes has functional consequences as increasing endosomal localization through mutations in tbc-2 reduced the lifespan of long-lived daf-2 IGFR mutants, depleted their fat stores, and DAF-16 target gene expression. Overall, this work identifies endosomal localization as a mechanism regulating DAF-16 FOXO, which is important for its functions in metabolism and aging.

We present the results of an intermediate-resolution (1.5\AA) spectroscopic study of 17 X-ray luminous narrow emission-line galaxies previously identified in the Cambridge-Cambridge {\it ROSAT} Serendipity Survey and the {\it Einstein} Extended Medium Sensitivity Survey. Emission-line ratios reveal that the sample is composed of ten Seyfert and seven starburst galaxies. Measured linewidths for the narrow H$\alpha$ emission lines lie in the range $170-460\,$km$\,$s$^{-1}$. Five of the objects show clear evidence for asymmetry in the [OIII]$\lambda$5007 emission-line profile. Broad H$\alpha$ emission is detected in six of the Seyfert galaxies, which range in type from Seyfert 1.5 to 2. Broad H$\beta$ emission is only detected in one Seyfert galaxy. The mean full width at half maximum for the broad lines in the Seyfert galaxies is ${\rm FWHM = 3900\pm 1750\,km\,s^{-1}}$. Broad (${\rm FWHM = 2200\pm 600\,km\,s^{-1}}$) $H\alpha$ emission is also detected in three of the starburst galaxies, which could originate from stellar winds or supernovae remnants. The mean Balmer decrement for the sample is H$\alpha$/H$\beta=3$, consistent with little or no reddening for the bulk of the sample. There is no evidence for any trend with X-ray luminosity in the ratio of starburst galaxies to Seyfert galaxies. Based on our previous observations, it is therefore likely that both classes of object comprise $\sim 10\,$per cent of the $2\,$keV X-ray background., Comment: uuencoded compressed postscript. The preprint is also available at URL http://www.ast.cam.ac.uk/preprint/PrePrint.html

The purposes of these experiments were to assess the effects of three variables on performance in extended periods of time without sleep: the effects of prior repetition of performance in such conditions, the effects of age and the effects of limited interjected sleep periods. A computer-based battery of performance tasks as used which included subjective measures, short and long term monitoring tasks, continuous production tasks, precision measures, and an extensive battery of cognitive tests. Repetition of extended performance across 48 hours without sleep at four monthly intervals did not offset performance decrements. Where effects were obtained, performance decrements were enhanced. In two experiments with 40-50 year old subjects and 50-60 year old subjects in extended performance of forty-eight hours without sleep, where differences were obtained, older subjects showed a greater performance degradation. Three schedules of interjected naps within a 72 hour period of extended were used: two hour naps prior to the second and third night period, two hours naps following the first and second night period; and a single four hour nap prior to the second night. Limited counter degradation effects were found in the final period of performance. The largest decrements on measures were found in subjective measures, vigilance tasks, and continuous production tasks. More limited decrements or no decrements were found in the cognitive tasks and the precision measures.