Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation

Frameshifting of mRNA during translation provides a strategy to expand the coding repertoire of cells and viruses. How and where in the elongation cycle +1-frameshifting occurs remains poorly understood. We describe seven ~3.5-A-resolution cryo-EM structures of 70S ribosome complexes, allowing visualization of elongation and translocation by the GTPase elongation factor G (EF-G). Four structures with a + 1-frameshifting-prone mRNA reveal that frameshifting takes place during translocation of tRNA and mRNA. Prior to EF-G binding, the pre-translocation complex features an in-frame tRNA-mRNA pairing in the A site. In the partially translocated structure with EF-G*GDPCP, the tRNA shifts to the +1-frame near the P site, rendering the freed mRNA base to bulge between the P and E sites and to stack on the 16S rRNA nucleotide G926. The ribosome remains frameshifted in the nearly post-translocation state. Our findings demonstrate that the ribosome and EF-G cooperate to induce +1 frameshifting during tRNA-mRNA translocation

Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice

<p>Abstract</p> <p>Background</p> <p>Inhibin is a tumor-suppressor and activin antagonist. Inhibin-deficient mice develop gonadal tumors and a cachexia wasting syndrome due to enhanced activin signaling. Because activins signal through SMAD2 and SMAD3 in vitro and loss of SMAD3 attenuates ovarian tumor development in inhibin-deficient females, we sought to determine the role of SMAD2 in the development of ovarian tumors originating from the granulosa cell lineage.</p> <p>Methods</p> <p>Using an inhibin α null mouse model and a conditional knockout strategy, double conditional knockout mice of Smad2 and inhibin alpha were generated in the current study. The survival rate and development of gonadal tumors and the accompanying cachexia wasting syndrome were monitored.</p> <p>Results</p> <p>Nearly identical to the controls, the Smad2 and inhibin alpha double knockout mice succumbed to weight loss, aggressive tumor progression, and death. Furthermore, elevated activin levels and activin-induced pathologies in the liver and stomach characteristic of inhibin deficiency were also observed in these mice. Our results indicate that SMAD2 ablation does not protect inhibin-deficient females from the development of ovarian tumors or the cachexia wasting syndrome.</p> <p>Conclusions</p> <p>SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin.</p

Favourable outcomes for the first 10 years of kidney and pancreas transplantation at Wits Donald Gordon Medical Centre, Johannesburg, South Africa

Background. It is important for centres participating in transplantation in South Africa (SA) to audit their outcomes. Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, SA, opened a transplant unit in 2004. The first 10 years of kidney and pancreas transplantation were reviewed to determine outcomes in respect of recipient and graft survival.Methods. A retrospective review was conducted of all kidney-alone and simultaneous kidney-pancreas (SKP) transplants performed at WDGMC from 1 January 2004 to 31 December 2013, with follow-up to 31 December 2014 to ensure at least 1 year of survival data. Information was accessed using the transplant registers and clinical records in the transplant clinic at WDGMC. The Kaplan-Meier method was used to estimate 1-, 5- and 10-year recipient and graft survival rates for primary (first graft) kidney-alone and SKP transplants.Results. The overall 10-year recipient and graft survival rates were 80.4% and 66.8%, respectively, for kidney-alone transplantation. In the kidney-alone group, children tended towards better recipient and graft survival compared with adults, but this was not statistically significant. In adults, recipient survival was significantly better for living than deceased donor type. Recipient and graft survival were significantly lower in black Africans than in the white (largest proportion in the sample) reference group. For SKP transplants, the 10-year recipient survival rate was 84.7%, while kidney and pancreas graft survival rates were 73.1% and 43.2%, respectively.Conclusion. Outcomes of the first 10 years of kidney and pancreas transplantation at WDGMC compare favourably with local and international survival data

The Global Landsat Archive: Status, Consolidation, and Direction

New and previously unimaginable Landsat applications have been fostered by a policy change in 2008 that made analysis-ready Landsat data free and open access. Since 1972, Landsat has been collecting images of the Earth, with the early years of the program constrained by onboard satellite and ground systems, as well as limitations across the range of required computing, networking, and storage capabilities. Rather than robust on-satellite storage for transmission via high bandwidth downlink to a centralized storage and distribution facility as with Landsat-8, a network of receiving stations, one operated by the U.S. government, the other operated by a community of International Cooperators (ICs), were utilized. ICs paid a fee for the right to receive and distribute Landsat data and over time, more Landsat data was held outside the archive of the United State Geological Survey (USGS) than was held inside, much of it unique. Recognizing the critical value of these data, the USGS began a Landsat Global Archive Consolidation (LGAC) initiative in 2010 to bring these data into a single, universally accessible, centralized global archive, housed at the Earth Resources Observation and Science (EROS) Center in Sioux Falls, South Dakota. The primary LGAC goals are to inventory the data held by ICs, acquire the data, and ingest and apply standard ground station processing to generate an L1T analysis-ready product. As of January 1, 2015 there were 5,532,454 images in the USGS archive. LGAC has contributed approximately 3.2 million of those images, more than doubling the original USGS archive holdings. Moreover, an additional 2.3 million images have been identified to date through the LGAC initiative and are in the process of being added to the archive. The impact of LGAC is significant and, in terms of images in the collection, analogous to that of having had twoadditional Landsat-5 missions. As a result of LGAC, there are regions of the globe that now have markedly improved Landsat data coverage, resulting in an enhanced capacity for mapping, monitoring change, and capturing historic conditions. Although future missions can be planned and implemented, the past cannot be revisited, underscoring the value and enhanced significance of historical Landsat data and the LGAC initiative. The aim of this paper is to report the current status of the global USGS Landsat archive, document the existing and anticipated contributions of LGAC to the archive, and characterize the current acquisitions of Landsat-7 and Landsat-8. Landsat-8 is adding data to the archive at an unprecedented rate as nearly all terrestrial images are now collected. We also offer key lessons learned so far from the LGAC initiative, plus insights regarding other critical elements of the Landsat program looking forward, such as acquisition, continuity, temporal revisit, and the importance of continuing to operationalize the Landsat program

Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP

During translation, a conserved GTPase elongation factor-EF-G in bacteria or eEF2 in eukaryotes-translocates tRNA and mRNA through the ribosome. EF-G has been proposed to act as a flexible motor that propels tRNA and mRNA movement, as a rigid pawl that biases unidirectional translocation resulting from ribosome rearrangements, or by various combinations of motor- and pawl-like mechanisms. Using time-resolved cryo-EM, we visualized GTP-catalyzed translocation without inhibitors, capturing elusive structures of ribosome•EF-G intermediates at near-atomic resolution. Prior to translocation, EF-G binds near peptidyl-tRNA, while the rotated 30S subunit stabilizes the EF-G GTPase center. Reverse 30S rotation releases Pi and translocates peptidyl-tRNA and EF-G by ~20 Å. An additional 4-Å translocation initiates EF-G dissociation from a transient ribosome state with highly swiveled 30S head. The structures visualize how nearly rigid EF-G rectifies inherent and spontaneous ribosomal dynamics into tRNA-mRNA translocation, whereas GTP hydrolysis and Pi release drive EF-G dissociation

Search for the Production of Element 112 in the 48Ca + 238U Reaction

We have searched for the production of element 112 in the reaction of 231 MeV 48Ca with 238U. We have not observed any events with a "one event" upper limit cross section of 1.6 pb for EVR-fission events and 1.8 pb for EVR-alpha events.Comment: 6 pages, 3 figures, submitted to Phys. Rev.