Punctuated Evolution Within a Eurythermic Genus (Mesenchytraeus) of Segmented Worms: Genetic Modification of the Glacier Ice Worm F1F0 ATP Synthase

Segmented worms (Annelida) are among the most successful animal inhabitants of extreme environments worldwide. An unusual group of Mesenchytraeus worms endemic to the Pacific Northwest of North America occupy geographically proximal ecozones ranging from low elevation temperate rainforests to high altitude glaciers. Along this altitudinal transect, Mesenchytraeus representatives from disparate habitat types were collected and subjected to deep mitochondrial and nuclear phylogenetic analyses. Evidence presented here employing modern bioinformatic analyses (i.e., maximum likelihood, Bayesian inference, multi-species coalescent) supports a Mesenchytraeus “explosion” in the upper Miocene (5-10 million years ago) that gave rise to ice, snow and terrestrial worms, derived from a common aquatic ancestor. Among these ecologically-disparate but genetically-close worms, those maintaining the highest intracellular ATP levels reside permanently on glacier ice (i.e., M. solifugus). A comparative molecular analysis of 11 core structural subunits of the F1Fo-ATP synthase revealed extraordinary conservation across species, with a few notable exceptions. Most strikingly, the ice worm mitochondrial-encoded ATP6 (a) subunit – the ATP throttle known to regulate proton flux, hence ATP synthesis – encoded a highly basic, 15 amino acid carboxy-terminal extension likely to have been acquired by lateral gene transfer from an ancestral prokaryote. This insertion is supported by transcriptome raw read reconstruction and independent PCR amplifications from three geographically-distinct ice worm populations, and represents a rare example of a mitochondrial-based gene transfer event. The position and biochemical properties of the extension domain suggest a role in ATP synthase dimerization and/or proton shuttling, both of which would predictably enhance ATP production

A Glutamine-Rich Factor Affects Stem Cell Genesis in Leech

Leech embryogenesis is a model for investigating cellular and molecular processes of development. Due to the unusually large size of embryonic stem cells (teloblasts: 50–300 μm) in the glossiphoniid leech, Theromyzon tessulatum, and the presence of identifiable stem cell precursors (proteloblasts), we previously isolated a group of genes upregulated upon stem cell birth. In the current study, we show that one of these genes, designated Theromyzon proliferation (Tpr), is required for normal stem cell genesis; specifically, transient Tpr knockdown experiments conducted with antisense oligonucleotides and monitored by semiquantitative RT-PCR, caused abnormal proteloblast proliferation leading to embryonic death, but did not overtly affect neuroectodermal or mesodermal stem cell development once these cells were born. Tpr encodes a large glutamine-rich (∼34%) domain that shares compositional similarity with strong transcriptional enhancers many of which have been linked with trinucleotide repeat disorders (e.g., Huntington's)

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

The SDSS-IV extended Baryon Oscillation Spectroscopic Survey : Luminous Red Galaxy Target Selection

We describe the algorithm used to select the Luminous Red Galaxy (LRG) sample for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV) using photometric data from both the SDSS and the Wide-Field Infrared Survey Explorer (WISE). LRG targets are required to meet a set of color selection criteria and have z-band and i-band MODEL magnitudes z <19.95 and 19.9 <i < 21.8, respectively. Our algorithm selects roughly 50 LRG targets per square degree, the great majority of which lie in the redshift range 0.6 <z <1.0 (median redshift 0.71). We demonstrate that our methods are highly effective at eliminating stellar contamination and lower-redshift galaxies. We perform a number of tests using spectroscopic data from SDSS-III/BOSS to determine the redshift reliability of our target selection and its ability to meet the science requirements of eBOSS. The SDSS spectra are of high enough signal-to-noise ratio that at least 89% of the target sample yields secure redshift measurements. We also present tests of the uniformity and homogeneity of the sample, demonstrating that it should be clean enough for studies of the large-scale structure of the universe at higher redshifts than SDSS-III/BOSS LRGs reached.Publisher PDFPeer reviewe

Understanding the complexity of disease-climate interactions for rice bacterial panicle blight under tropical conditions

Bacterial panicle blight (BPB) caused by Burkholderia glumae is one of the main concerns for rice production in the Americas since bacterial infection can interfere with the grain-filling process and under severe conditions can result in high sterility. B. glumae has been detected in several rice-growing areas of Colombia and other countries of Central and Andean regions in Latin America, although evidence of its involvement in decreasing yield under these conditions is lacking. Analysis of different parameters in trials established in three rice-growing areas showed that, despite BPB presence, severity did not explain the sterility observed in fields. PCR tests for B. glumae confirmed low infection in all sites and genotypes, only 21.4% of the analyzed samples were positive for B. glumae. Climate parameters showed that Montería and Saldaña registered maximum temperature above 34°C, minimum temperature above 23°C, and Relative Humidity above 80%, conditions that favor the invasion model described for this pathogen in Asia. Our study found that in Colombia, minimum temperature above 23°C during 10 days after flowering is the condition that correlates with disease incidence. Therefore, this correlation, and the fact that Montería and Saldaña had a higher level of infected samples according to PCR tests, high minimum temperature, but not maximum temperature, seems to be determinant for B. glumae colonization under studied field conditions. This knowledge is a solid base line to design strategies for disease control, and is also a key element for breeders to develop strategies aimed to decrease the effect of B. glumae and high night-temperature on rice yield under tropical conditions

Oncolytic DNX-2401 Virotherapy Plus Pembrolizumab in Recurrent Glioblastoma: A Phase 1/2 Trial

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients

Structural basis for VPS34 kinase activation by Rab1 and Rab5 on membranes.

The lipid phosphatidylinositol-3-phosphate (PI3P) is a regulator of two fundamental but distinct cellular processes, endocytosis and autophagy, so its generation needs to be under precise temporal and spatial control. PI3P is generated by two complexes that both contain the lipid kinase VPS34: complex II on endosomes (VPS34/VPS15/Beclin 1/UVRAG), and complex I on autophagosomes (VPS34/VPS15/Beclin 1/ATG14L). The endosomal GTPase Rab5 binds complex II, but the mechanism of VPS34 activation by Rab5 has remained elusive, and no GTPase is known to bind complex I. Here we show that Rab5a-GTP recruits endocytic complex II to membranes and activates it by binding between the VPS34 C2 and VPS15 WD40 domains. Electron cryotomography of complex II on Rab5a-decorated vesicles shows that the VPS34 kinase domain is released from inhibition by VPS15 and hovers over the lipid bilayer, poised for catalysis. We also show that the GTPase Rab1a, which is known to be involved in autophagy, recruits and activates the autophagy-specific complex I, but not complex II. Both Rabs bind to the same VPS34 interface but in a manner unique for each. These findings reveal how VPS34 complexes are activated on membranes by specific Rab GTPases and how they are recruited to unique cellular locations

Earnings Benefits of Tulsa's Pre-K Program for Different Income Groups

This paper estimates future adult earnings effects associated with a universal pre-K program in Tulsa, Oklahoma. These informed projections help to compensate for the lack of long-term data on universal pre-K programs, while using metrics that relate test scores to valued social benefits. Combining test-score data from the fall of 2006 and recent findings by Chetty et al. (forthcoming) on the relationship between kindergarten test scores and adult earnings, we generate plausible projections of adult earnings effects and a partial cost-benefit analysis of the Tulsa pre-K program. We find substantial projected earnings benefits for program participants who differ by income and by program dosage. The dollar effects and benefit-cost ratios are similar across groups, with benefit-to-cost ratios of approximately 3 or 4 to 1. Because we only consider adult earnings benefits, actual benefit-cost ratios are likely higher, especially for disadvantaged children