Allosteric collaboration between elongation factor G and the ribosomal L1 stalk directs tRNA movements during translation

Determining the mechanism by which transfer RNAs (tRNAs) rapidly and precisely transit through the ribosomal A, P and E sites during translation remains a major goal in the study of protein synthesis. Here, we report the real-time dynamics of the L1 stalk, a structural element of the large ribosomal subunit that is implicated in directing tRNA movements during translation. Within pre-translocation ribosomal complexes, the L1 stalk exists in a dynamic equilibrium between open and closed conformations. Binding of elongation factor G (EF-G) shifts this equilibrium towards the closed conformation through one of at least two distinct kinetic mechanisms, where the identity of the P-site tRNA dictates the kinetic route that is taken. Within post-translocation complexes, L1 stalk dynamics are dependent on the presence and identity of the E-site tRNA. Collectively, our data demonstrate that EF-G and the L1 stalk allosterically collaborate to direct tRNA translocation from the P to the E sites, and suggest a model for the release of E-site tRNA

Hierarchically-coupled hidden Markov models for learning kinetic rates from single-molecule data

We address the problem of analyzing sets of noisy time-varying signals that all report on the same process but confound straightforward analyses due to complex inter-signal heterogeneities and measurement artifacts. In particular we consider single-molecule experiments which indirectly measure the distinct steps in a biomolecular process via observations of noisy time-dependent signals such as a fluorescence intensity or bead position. Straightforward hidden Markov model (HMM) analyses attempt to characterize such processes in terms of a set of conformational states, the transitions that can occur between these states, and the associated rates at which those transitions occur; but require ad-hoc post-processing steps to combine multiple signals. Here we develop a hierarchically coupled HMM that allows experimentalists to deal with inter-signal variability in a principled and automatic way. Our approach is a generalized expectation maximization hyperparameter point estimation procedure with variational Bayes at the level of individual time series that learns an single interpretable representation of the overall data generating process.Comment: 9 pages, 5 figure

Acoustic sensor engineering evaluation test report

Two types of one-inch diameter sound pressure level sensors, which are candidates for monitoring ambient noise in the shuttle orbiter crew compartment during rest periods, were exposed to temperature, passive humidity, and vibration. One unexposed sensor of each type served as a reference unit. Except for the humidity exposures, each of the three capacitive microphones was individually tested in sequence with the essential voltage power supply and preamplifier. One unit exibited anomalous characteristics after the humidity exposure but returned to normal after being dried in an oven at 115 deg for two hours. Except for the humidity exposures, each of the three piezoelectric microphones was individually tested with a laboratory type amplifier. Two apparent failures occurred during these tests. The diaphragm on one was found ruptured after the fourth cycle of the humidity test. A second sensor showed an anomaly after the random vibration tests at which time its sensitivity was consistent at about one-half its former value

OncoLog, Volume 59, Number 02, February 2014

New Approaches Revolutionize the Treatment of Advanced Melanoma: Recent breakthroughs in immunotherapy and targeted therapy have improved outcomes for patients with advanced melanoma Comprehensive Tobacco Treatment Approach Helps Patients Quit on Their Terms: Kicking a tobacco habit is a formidable task. Quitting tobacco after a diagnosis of cancer, can be even more difficult Targeted Drug Shows Promise Against Advanced Breast Cancer: Adding the experimental kinase inhibitor palbociclib to standard hormonal therapy may delay disease progression in patients with advanced breast cancer that is estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER@) negative HOUSE CALL: Avoiding Food-Drug Interactions: Some foods and medicines don’t mix INBRIEF: PKM2 Identified as Potential Prognostic Marker for Glioblastomahttps://openworks.mdanderson.org/oncolog/1241/thumbnail.jp

Limited-Access Bioremediation in a Factory Setting

A factory in New Hampshire had a volatile organic compound (VOC) release detected in a storm-water outfall pipe. Hydrogen Release Compound (HRC) injection was determined to be the best remedial solution. Tight soils, shallow water table, access limitations, and pending property sale complicated remediation. Groundwater was directly below the floor slab. The plume was centered on the storm-water drain which carries runoff from the upgradient parking lot under the building. The VOCs are believed to have entered the subsurface in the central area of the building through spillage; the storm drain system was a preferential pathway. The groundwater contamination was addressed through bioremediation using HRC. Application required many injection points and applications, due to the low permeability of the soil. Due to interference with operations and property sale, repeated openings of the floor for injections using a drill rig were not feasible. Permanent injection points were installed, but would not be accessible for direct injection. Therefore, a trench was cut into the concrete floor slab between each point and the wall. Piping ran from the injection point to the wall, terminating at a standpipe with a quick-connect fitting. Each trench was then fillled with concrete to restore the floor slab. Since starting HRC treatment, VOC levels at the outfall have dropped to below the state regulatory standard. One well had levels of 1800 ug/L and 1200 ug/L of Cis-1,2 Dichloroethene and Vinyl Chloride in April, 2008. By January, 2009, both were below MCLs. Site closure is expected to be completed in a reasonable timeframe. The treatment has not interfered with Site activities or with sale of the Site

Brown Stem Rot and its Interaction with the Soybean Cyst Nematode

Brown stem rot (BSR) of soybeans is caused by the fungal vascular pathogen Cadophora gregata (previously named Phialophora gregata). BSR is an economically important disease of soybeans in the north central United States, being prevalent in 68 to 73% of the soybean fields of Illinois, Iowa, and Minnesota (Workneh et al. 1999). There are two genetic types (called genotypes) of C. gregata that differ in their ability to cause foliar symptoms on susceptible soybeans (Chen et al. 2000). Infection by genotype A of the fungus can result in mild to severe brown discoloration of the pith and severe foliar symptoms on susceptible soybeans and mild or no foliar symptom on resistant soybeans. In contrast, infection by genotype B of the fungus causes mild to severe brown discoloration of the pith, but mild or no foliar symptoms. Soybeans can be colonized by both genotypes of the fungus without exhibiting stem or foliar symptoms (Taboret al. 2003a). Consequently, hidden yield loss due to BSR may frequently occur