Loss of Prox1

Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease

Evaluating Cumulative Ecosystem Response to Restoration Projects in the Lower Columbia River and Estuary, 2009

This is the sixth annual report of a seven-year project (2004 through 2010) to evaluate the cumulative effects of habitat restoration actions in the lower Columbia River and estuary (LCRE). The project, called the Cumulative Effects Study, is being conducted for the U.S. Army Corps of Engineers Portland District (USACE) by the Marine Sciences Laboratory of the Pacific Northwest National Laboratory (PNNL), the Pt. Adams Biological Field Station of the National Marine Fisheries Service (NMFS), the Columbia River Estuary Study Taskforce (CREST), and the University of Washington. The goal of the Cumulative Effects Study is to develop a methodology to evaluate the cumulative effects of multiple habitat restoration projects intended to benefit ecosystems supporting juvenile salmonids in the 235-km-long LCRE. Literature review in 2004 revealed no existing methods for such an evaluation and suggested that cumulative effects could be additive or synergistic. From 2005 through 2009, annual field research involved intensive, comparative studies paired by habitat type (tidal swamp versus marsh), trajectory (restoration versus reference site), and restoration action (tidegate replacement vs. culvert replacement vs. dike breach)

A First Comparison of Kepler Planet Candidates in Single and Multiple Systems

In this letter we present an overview of the rich population of systems with multiple candidate transiting planets found in the first four months of Kepler data. The census of multiples includes 115 targets that show 2 candidate planets, 45 with 3, 8 with 4, and 1 each with 5 and 6, for a total of 170 systems with 408 candidates. When compared to the 827 systems with only one candidate, the multiples account for 17 percent of the total number of systems, and a third of all the planet candidates. We compare the characteristics of candidates found in multiples with those found in singles. False positives due to eclipsing binaries are much less common for the multiples, as expected. Singles and multiples are both dominated by planets smaller than Neptune; 69 +2/-3 percent for singles and 86 +2/-5 percent for multiples. This result, that systems with multiple transiting planets are less likely to include a transiting giant planet, suggests that close-in giant planets tend to disrupt the orbital inclinations of small planets in flat systems, or maybe even to prevent the formation of such systems in the first place.Comment: 13 pages, 13 figures, submitted to ApJ Letter

High-Input Management Systems Effect on Soybean Seed Yield, Yield Components, and Economic Break-Even Probabilities

Elevated soybean [Glycine max (L.) Merr.] prices have spurred interest in maximizing soybean seed yield and has led growers to increase the number of inputs in their production systems. However, little information exists about the effects of high-input management on soybean yield and profitability. The purpose of this study was to investigate the effects of individual inputs, as well as combinations of inputs marketed to protect or increase soybean seed yield, yield components, and economic break-even probabilities. Studies were established in nine states and three soybean growing regions (North, Central, and South) between 2012 and 2014. In each site-year both individual inputs and combination high-input (SOYA) management systems were tested. When averaged between 2012 and 2014, regional results showed no seed yield responses in the South region, but multiple inputs affected seed yield in the North region. In general, the combination SOYA inputs resulted in the greatest yield increases (up to 12%) compared to standard management, but Bayesian economic analysis indicated SOYA had low break-even probabilities. Foliar insecticide had the greatest break-even probabilities across all environments, although insect pressure was generally low across all site-years. Soybean producers in North region are likely to realize a greater response from increased inputs, but producers across all regions should carefully evaluate adding inputs to their soybean management systems and ensure that they continue to follow the principles of integrated pest management

Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA

First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec spectrograph. The MINERVA mission is to discover super-Earths in the habitable zones of nearby stars. This can be accomplished with MINERVA's unique combination of high precision and high cadence over long time periods. In this work, we detail changes to the MINERVA facility that have occurred since our previous paper. We then describe MINERVA's robotic control software, the process by which we perform 1D spectral extraction, and our forward modeling Doppler pipeline. In the process of improving our forward modeling procedure, we found that our spectrograph's intrinsic instrumental profile is stable for at least nine months. Because of that, we characterized our instrumental profile with a time-independent, cubic spline function based on the profile in the cross dispersion direction, with which we achieved a radial velocity precision similar to using a conventional "sum-of-Gaussians" instrumental profile: 1.8 m s$^{-1}$ over 1.5 months on the RV standard star HD 122064. Therefore, we conclude that the instrumental profile need not be perfectly accurate as long as it is stable. In addition, we observed 51 Peg and our results are consistent with the literature, confirming our spectrograph and Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte

Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor

The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier

Characterizing Genotype X Management Interactions on Soybean Seed Yield

Increased soybean [Glycine max (L.) Merr.] commodity prices in recent years have generated interest in high-input systems to increase yield. The objective of this study was to evaluate the effects of current, high-yielding cultivars under high- and low-input systems on soybean yield and yield components. Research trials were conducted at 19 locations spanning nine states from 2012 to 2014. At each location, six high-yielding cultivars were grown under three input systems: (i) standard practice (SP, current recommended practices), (ii) high-input treatment consisting of a seed treatment fungicide, insecticide, nematistat, inoculant, and lipo-chitooligosaccharide (LCO); soil-applied N fertilizer; foliar LCO, fertilizer, antioxidant, fungicide and insecticide (SOYA), and (iii) SOYA minus foliar fungicide (SOYA-FF). An individual site-year yield analysis found only 3 of 53 (5.7%) site-years examined had a significant cultivar × input system interaction, suggesting cultivar selection and input system decisions can remain independent. Across all site-years, the SOYA and SOYA-FF treatments yielded 231 (5.5%) and 147 kg ha–1 (3.5%) more than the SP, and input system differences were found among maturity groups. Yield component measurements (seeds m–2, seed mass, early-season and final plant stand, pods plant–1, and seeds pod–1) indicated positive yield responses were due to increased seeds m–2 and seed mass. While both high-input systems increased yield on average, grower return on investment (ROI) would be negative given today’s commodity prices. These results further support the use of integrated pest management principles for making input decisions instead of using prophylactic applications to maximize soybean yield and profitability