Choosing a genome browser for a Model Organism Database: surveying the Maize community

As the B73 maize genome sequencing project neared completion, MaizeGDB began to integrate a graphical genome browser with its existing web interface and database. To ensure that maize researchers would optimally benefit from the potential addition of a genome browser to the existing MaizeGDB resource, personnel at MaizeGDB surveyed researchers’ needs. Collected data indicate that existing genome browsers for maize were inadequate and suggest implementation of a browser with quick interface and intuitive tools would meet most researchers’ needs. Here, we document the survey’s outcomes, review functionalities of available genome browser software platforms and offer our rationale for choosing the GBrowse software suite for MaizeGDB. Because the genome as represented within the MaizeGDB Genome Browser is tied to detailed phenotypic data, molecular marker information, available stocks, etc., the MaizeGDB Genome Browser represents a novel mechanism by which the researchers can leverage maize sequence information toward crop improvement directly

Induction of Liver Steatosis and Lipid Droplet Formation in ATF6α-Knockout Mice Burdened with Pharmacological Endoplasmic Reticulum Stress

We burdened mice with intraperitoneal injection of the endoplasmic reticulum stress-inducing reagent tunicamycin, and found that wild-type mice were able to recover from the insult, whereas ATF6α-knockout mice exhibited liver dysfunction and steatosis. Our results establish links between endoplasmic reticulum stress, lipid metabolism and steatosi

Phenotypic and Genome-Wide Analysis of an Antibiotic-Resistant Small Colony Variant (SCV) of Pseudomonas aeruginosa

Small colony variants (SCVs) are slow-growing bacteria, which often show increased resistance to antibiotics and cause latent or recurrent infections. It is therefore important to understand the mechanisms at the basis of this phenotypic switch.One SCV (termed PAO-SCV) was isolated, showing high resistance to gentamicin and to the cephalosporine cefotaxime. PAO-SCV was prone to reversion as evidenced by emergence of large colonies with a frequency of 10(-5) on media without antibiotics while it was stably maintained in presence of gentamicin. PAO-SCV showed a delayed growth, defective motility, and strongly reduced levels of the quorum sensing Pseudomonas quinolone signal (PQS). Whole genome expression analysis further suggested a multi-layered antibiotic resistance mechanism, including simultaneous over-expression of two drug efflux pumps (MexAB-OprM, MexXY-OprM), the LPS modification operon arnBCADTEF, and the PhoP-PhoQ two-component system. Conversely, the genes for the synthesis of PQS were strongly down-regulated in PAO-SCV. Finally, genomic analysis revealed the presence of mutations in phoP and phoQ genes as well as in the mexZ gene encoding a repressor of the mexXY and mexAB-oprM genes. Only one mutation occurred only in REV, at nucleotide 1020 of the tufA gene, a paralog of tufB, both encoding the elongation factor Tu, causing a change of the rarely used aspartic acid codon GAU to the more common GAC, possibly causing an increase of tufA mRNA translation. High expression of phoP and phoQ was confirmed for the SCV variant while the revertant showed expression levels reduced to wild-type levels.By combining data coming from phenotypic, gene expression and proteome analysis, we could demonstrate that resistance to aminoglycosides in one SCV mutant is multifactorial including overexpression of efflux mechanisms, LPS modification and is accompanied by a drastic down-regulation of the Pseudomonas quinolone signal quorum sensing system

Monitoring the Morphology of M87* in 2009–2017 with the Event Horizon Telescope

The Event Horizon Telescope (EHT) has recently delivered the first resolved images of M87*, the supermassive black hole in the center of the M87 galaxy. These images were produced using 230 GHz observations performed in 2017 April. Additional observations are required to investigate the persistence of the primary image feature—a ring with azimuthal brightness asymmetry—and to quantify the image variability on event horizon scales. To address this need, we analyze M87* data collected with prototype EHT arrays in 2009, 2011, 2012, and 2013. While these observations do not contain enough information to produce images, they are sufficient to constrain simple geometric models. We develop a modeling approach based on the framework utilized for the 2017 EHT data analysis and validate our procedures using synthetic data. Applying the same approach to the observational data sets, we find the M87* morphology in 2009–2017 to be consistent with a persistent asymmetric ring of ~40 μas diameter. The position angle of the peak intensity varies in time. In particular, we find a significant difference between the position angle measured in 2013 and 2017. These variations are in broad agreement with predictions of a subset of general relativistic magnetohydrodynamic simulations. We show that quantifying the variability across multiple observational epochs has the potential to constrain the physical properties of the source, such as the accretion state or the black hole spin

First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole

We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 +/- 3 mu as and constrain its fractional width to b

First M87 Event Horizon Telescope Results. VI. The Shadow and Mass of the Central Black Hole

We present measurements of the properties of the central radio source in M87 using Event Horizon Telescope data obtained during the 2017 campaign. We develop and fit geometric crescent models (asymmetric rings with interior brightness depressions) using two independent sampling algorithms that consider distinct representations of the visibility data. We show that the crescent family of models is statistically preferred over other comparably complex geometric models that we explore. We calibrate the geometric model parameters using general relativistic magnetohydrodynamic (GRMHD) models of the emission region and estimate physical properties of the source. We further fit images generated from GRMHD models directly to the data. We compare the derived emission region and black hole parameters from these analyses with those recovered from reconstructed images. There is a remarkable consistency among all methods and data sets. We find that >50% of the total flux at arcsecond scales comes from near the horizon, and that the emission is dramatically suppressed interior to this region by a factor >10, providing direct evidence of the predicted shadow of a black hole. Across all methods, we measure a crescent diameter of 42 +/- 3 mu as and constrain its fractional width to be <0.5. Associating the crescent feature with the emission surrounding the black hole shadow, we infer an angular gravitational radius of GM/Dc(2) = 3.8 +/- 0.4 mu as. Folding in a distance measurement of 16.8(-0.7)(+0.8) gives a black hole mass of M = 6.5. 0.2 vertical bar(stat) +/- 0.7 vertical bar(sys) x 10(9) M-circle dot. This measurement from lensed emission near the event horizon is consistent with the presence of a central Kerr black hole, as predicted by the general theory of relativity

First M87 Event Horizon Telescope Results. IV. Imaging the Central Supermassive Black Hole

We present the first Event Horizon Telescope (EHT) images of M87, using observations from April 2017 at 1.3 mm wavelength. These images show a prominent ring with a diameter of similar to 40 mu as, consistent with the size and shape of the lensed photon orbit encircling the "shadow" of a supermassive black hole. The ring is persistent across four observing nights and shows enhanced brightness in the south. To assess the reliability of these results, we implemented a two-stage imaging procedure. In the first stage, four teams, each blind to the others' work, produced images of M87 using both an established method (CLEAN) and a newer technique (regularized maximum likelihood). This stage allowed us to avoid shared human bias and to assess common features among independent reconstructions. In the second stage, we reconstructed synthetic data from a large survey of imaging parameters and then compared the results with the corresponding ground truth images. This stage allowed us to select parameters objectively to use when reconstructing images of M87. Across all tests in both stages, the ring diameter and asymmetry remained stable, insensitive to the choice of imaging technique. We describe the EHT imaging procedures, the primary image features in M87, and the dependence of these features on imaging assumptions

A Universal Power-law Prescription for Variability from Synthetic Images of Black Hole Accretion Flows

We present a framework for characterizing the spatiotemporal power spectrum of the variability expected from the horizon-scale emission structure around supermassive black holes, and we apply this framework to a library of general relativistic magnetohydrodynamic (GRMHD) simulations and associated general relativistic ray-traced images relevant for Event Horizon Telescope (EHT) observations of Sgr A*. We find that the variability power spectrum is generically a red-noise process in both the temporal and spatial dimensions, with the peak in power occurring on the longest timescales and largest spatial scales. When both the time-averaged source structure and the spatially integrated light-curve variability are removed, the residual power spectrum exhibits a universal broken power-law behavior. On small spatial frequencies, the residual power spectrum rises as the square of the spatial frequency and is proportional to the variance in the centroid of emission. Beyond some peak in variability power, the residual power spectrum falls as that of the time-averaged source structure, which is similar across simulations; this behavior can be naturally explained if the variability arises from a multiplicative random field that has a steeper high-frequency power-law index than that of the time-averaged source structure. We briefly explore the ability of power spectral variability studies to constrain physical parameters relevant for the GRMHD simulations, which can be scaled to provide predictions for black holes in a range of systems in the optically thin regime. We present specific expectations for the behavior of the M87* and Sgr A* accretion flows as observed by the EHT

A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted by the WIN consortium, aiming to significantly impact survival in metastatic NSCLC and other malignancies