The undertranslated transcriptome reveals widespread translational silencing by alternative 5' transcript leaders

BACKGROUND: Translational efficiencies in Saccharomyces cerevisiae vary from transcript to transcript by approximately two orders of magnitude. Many of the poorly translated transcripts were found to respond to the appropriate external stimulus by recruiting ribosomes. Unexpectedly, a high frequency of these transcripts showed the appearance of altered 5' leaders that coincide with increased ribosome loading. RESULTS: Of the detectable transcripts in S. cerevisiae, 8% were found to be underloaded with ribosomes. Gene ontology categories of responses to stress or external stimuli were overrepresented in this population of transcripts. Seventeen poorly loaded transcripts involved in responses to pheromone, nitrogen starvation, and osmotic stress were selected for detailed study and were found to respond to the appropriate environmental signal with increased ribosome loading. Twelve of these regulated transcripts exhibited structural changes in their 5' transcript leaders in response to the environmental signal. In many of these the coding region remained intact, whereas regulated shortening of the 5' end truncated the open reading frame in others. Colinearity between the gene and transcript sequences eliminated regulated splicing as a mechanism for these alterations in structure. CONCLUSION: Frequent occurrence of coordinated changes in transcript structure and translation efficiency, in at least three different gene regulatory networks, suggests a widespread phenomenon. It is likely that many of these altered 5' leaders arose from changes in promoter usage. We speculate that production of translationally silenced transcripts may be one mechanism for allowing low-level transcription activity necessary for maintaining an open chromatin structure while not allowing inappropriate protein production

Development of a Passive and Slope Adaptable Prosthetic Foot

Historically, users of prosthetic ankles have relied on actively operated systems to provide effective slope adaptability. However, there are many drawbacks to these systems. This research builds upon work previously completed by Hansen et al. as it develops a passive, hydraulically operated prosthetic ankle with the capability of adapting to varying terrain in every step. Using gait cycle data and an analysis of ground reaction forces, the team determined that weight activation was the most effective way to activate the hydraulic circuit. Evaluations of the system pressure and energy showed that although the spring damper system results in a loss of 9J of energy to the user, the footplate stores 34J more than a standard prosthesis. Therefore, the hydraulic prosthetic provides a 54% increase in stored energy when compared to a standard prosthesis. The hydraulic circuit manifold prototype was manufactured and tested. Through proof of concept testing, the prototype proved to be slope adaptable by successfully achieving a plantarflexion angle of 16 degrees greater than a standard prosthetic foot currently available on the market.Massachusetts Institute of Technology. Tata Center for Technology and Desig

A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm

The twentieth century was marked by extraordinary advances in our understanding of microbes and infectious disease, but pandemics remain, food and waterborne illnesses are frequent, multidrug-resistant microbes are on the rise, and the needed drugs and vaccines have not been developed. The scientific approaches of the past—including the intense focus on individual genes and proteins typical of molecular biology—have not been sufficient to address these challenges. The first decade of the twenty-first century has seen remarkable innovations in technology and computational methods. These new tools provide nearly comprehensive views of complex biological systems and can provide a correspondingly deeper understanding of pathogen-host interactions. To take full advantage of these innovations, the National Institute of Allergy and Infectious Diseases recently initiated the Systems Biology Program for Infectious Disease Research. As participants of the Systems Biology Program, we think that the time is at hand to redefine the pathogen-host research paradigm

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove

The Allen Telescope Array Twenty-centimeter Survey - A 690-Square-Degree, 12-Epoch Radio Dataset - I: Catalog and Long-Duration Transient Statistics

We present the Allen Telescope Array Twenty-centimeter Survey (ATATS), a multi-epoch (12 visits), 690 square degree radio image and catalog at 1.4GHz. The survey is designed to detect rare, very bright transients as well as to verify the capabilities of the ATA to form large mosaics. The combined image using data from all 12 ATATS epochs has RMS noise sigma = 3.94mJy / beam and dynamic range 180, with a circular beam of 150 arcsec FWHM. It contains 4408 sources to a limiting sensitivity of S = 20 mJy / beam. We compare the catalog generated from this 12-epoch combined image to the NRAO VLA Sky Survey (NVSS), a legacy survey at the same frequency, and find that we can measure source positions to better than ~20 arcsec. For sources above the ATATS completeness limit, the median flux density is 97% of the median value for matched NVSS sources, indicative of an accurate overall flux calibration. We examine the effects of source confusion due to the effects of differing resolution between ATATS and NVSS on our ability to compare flux densities. We detect no transients at flux densities greater than 40 mJy in comparison with NVSS, and place a 2-sigma upper limit on the transient rate for such sources of 0.004 per square degree. These results suggest that the > 1 Jy transients reported by Matsumura et al. (2009) may not be true transients, but rather variable sources at their flux density threshold.Comment: 41 pages, 19 figures, ApJ accepted; corrected minor typo in Table