Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of \u3cem\u3eFARS2\u3c/em\u3e-linked Disease

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins

Editing of Misaminoacylated tRNA Controls the Sensitivity of Amino Acid Stress Responses in Saccharomyces cerevisiae

Amino acid starvation activates the protein kinase Gcn2p, leading to changes in gene expression and translation. Gcn2p is activated by deacylated tRNA, which accumulates when tRNA aminoacylation is limited by lack of substrates or inhibition of synthesis. Pairing of amino acids and deacylated tRNAs is catalyzed by aminoacyl-tRNA synthetases, which use quality control pathways to maintain substrate specificity. Phenylalanyl-tRNA synthetase (PheRS) maintains specificity via an editing pathway that targets non-cognate Tyr-tRNAPhe. While the primary role of aaRS editing is to prevent misaminoacylation, we demonstrate editing of misaminoacylated tRNA is also required for detection of amino acid starvation by Gcn2p. Ablation of PheRS editing caused accumulation of Tyr-tRNAPhe (5%), but not deacylated tRNAPhe during amino acid starvation, limiting Gcn2p kinase activity and suppressing Gcn4p-dependent gene expression. While the PheRS-editing ablated strain grew 50% slower and displayed a 27-fold increase in the rate of mistranslation of Phe codons as Tyr compared to wild type, the increase in mistranslation was insufficient to activate an unfolded protein stress response. These findings show that during amino acid starvation a primary role of aaRS quality control is to help the cell mount an effective stress response, independent of the role of editing in maintaining translational accuracy

Ligand Specificity and Affinity in the Sulforhodamine B Binding RNA Aptamer

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.bbrc.2020.06.056. © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Binding affinity and selectivity are critical properties of aptamers that must be optimized for any application. The sulforhodamine B binding RNA aptamer (SRB‐2) is a somewhat promiscuous aptamer that can bind ligands that vary markedly in shape, size and charge. Here we categorize potential ligands based on their binding mode and structural characteristics required for high affinity and selectivity. Several known and potential ligands of SRB‐2 were screened for binding affinity using LSPR, ITC and NMR spectroscopy. The study shows that rhodamine B has the ideal structural and electrostatic properties for selective and high‐affinity binding of the SRB‐2 aptamer.NSERC Discovery Grant 30345

A low-dissipation, pumpless, gravity-induced flow battery

Redox flow batteries have the potential to provide low-cost energy storage to enable renewable energy technologies such as wind and solar to overcome their inherent intermittency and to improve the efficiency of electric grids. Conventional flow batteries are complex electromechanical systems designed to simultaneously control flow of redox active fluids and perform electrochemical functions. With the advent of redox active fluids with high capacity density, i.e., Faradaic capacity significantly exceeding the 1–2 M concentration equivalents typical of aqueous redox flow batteries, new flow battery designs become of interest. Here, we design and demonstrate a proof-of-concept prototype for a “gravity-induced flow cell” (GIFcell), representing one of a family of approaches to simpler, more robust, passively driven, lower-cost flow battery architectures. Such designs are particularly appropriate for semi-solid electrodes comprising suspensions of networked conductors and/or electroactive particles, due to their low energy dissipation during flow. Accordingly, we demonstrate the GIFcell using nonaqueous lithium polysulfide solutions containing a nanoscale carbon network in a half-flow-cell configuration and achieve round trip energy efficiency as high as 91%

Galaxy And Mass Assembly (GAMA): Self-Organizing Map Application on Nearby Galaxies

Galaxy populations show bimodality in a variety of properties: stellar mass, colour, specific star-formation rate, size, and S\'ersic index. These parameters are our feature space. We use an existing sample of 7556 galaxies from the Galaxy and Mass Assembly (GAMA) survey, represented using five features and the K-means clustering technique, showed that the bimodalities are the manifestation of a more complex population structure, represented by between 2 and 6 clusters. Here we use Self Organizing Maps (SOM), an unsupervised learning technique which can be used to visualize similarity in a higher dimensional space using a 2D representation, to map these five-dimensional clusters in the feature space onto two-dimensional projections. To further analyze these clusters, using the SOM information, we agree with previous results that the sub-populations found in the feature space can be reasonably mapped onto three or five clusters. We explore where the "green valley" galaxies are mapped onto the SOM, indicating multiple interstitial populations within the green valley population. Finally, we use the projection of the SOM to verify whether morphological information provided by GalaxyZoo users, for example, if features are visible, can be mapped onto the SOM-generated map. Voting on whether galaxies are smooth, likely ellipticals, or "featured" can reasonably be separated but smaller morphological features (bar, spiral arms) can not. SOMs promise to be a useful tool to map and identify instructive sub-populations in multidimensional galaxy survey feature space, provided they are large enough.Comment: 14 pages, 14 figures, accepted by MNRA

Galaxy and mass assembly (GAMA): Self-Organizing Map application on nearby galaxies

Galaxy populations show bimodality in a variety of properties: stellar mass, colour, specific star-formation rate, size, and Sérsic index. These parameters are our feature space. We use an existing sample of 7556 galaxies from the Galaxy and Mass Assembly (GAMA) survey, represented using five features and the K-means clustering technique, showed that the bimodalities are the manifestation of a more complex population structure, represented by between two and six clusters. Here we use Self-Organizing Maps (SOM), an unsupervised learning technique that can be used to visualize similarity in a higher dimensional space using a 2D representation, to map these 5D clusters in the feature space on to 2D projections. To further analyse these clusters, using the SOM information, we agree with previous results that the sub-populations found in the feature space can be reasonably mapped on to three or five clusters. We explore where the ‘green valley’ galaxies are mapped on to the SOM, indicating multiple interstitial populations within the green valley population. Finally, we use the projection of the SOM to verify whether morphological information provided by GalaxyZoo users, for example, if features are visible, can be mapped on to the SOM-generated map. Voting on whether galaxies are smooth, likely ellipticals, or ‘featured’ can reasonably be separated but smaller morphological features (bar, spiral arms) can not. SOMs promise to be a useful tool to map and identify instructive sub-populations in multidimensional galaxy survey feature space, provided they are large enough

History of Galaxy Interactions and their Impact on Star Formation over the Last 7 Gyr from GEMS

We perform a comprehensive estimate of the frequency of galaxy mergers and their impact on star formation over z~0.24--0.80 (lookback time T_b~3--7 Gyr) using 3698 (M*>=1e9 Msun) galaxies with GEMS HST, COMBO-17, and Spitzer data. Our results are: (1) Among 790 high mass (M*>=2.5e10 Msun) galaxies, the visually-based merger fraction over z~0.24--0.80, ranges from 9%+-5% to 8%+-2%. Lower limits on the major and minor merger fractions over this interval range from 1.1% to 3.5%, and 3.6% to 7.5%, respectively. This is the first approximate empirical estimate of the frequency of minor mergers at z<1. For a visibility timescale of ~0.5 Gyr, it follows that over T_b~3--7 Gyr, ~68% of high mass systems have undergone a merger of mass ratio >1/10, with ~16%, 45%, and 7% of these corresponding respectively to major, minor, and ambiguous `major or minor' mergers. The mean merger rate is a few x 1e-4 Gyr-1 Mpc-3. (2) We compare the empirical merger fraction and rate for high mass galaxies to a suite of Lambda CDM-based models: halo occupation distribution models, semi-analytic models, and hydrodynamic SPH simulations. We find qualitative agreement between observations and models such that the (major+minor) merger fraction or rate from different models bracket the observations, and show a factor of five dispersion. Near-future improvements can now start to rule out certain merger scenarios. (3) Among ~3698 M*>=1e9 Msun galaxies, we find that the mean SFR of visibly merging systems is only modestly enhanced compared to non-interacting galaxies over z~0.24--0.80. Visibly merging systems only account for less than 30% of the cosmic SFR density over T_b~3--7 Gyr. This suggests that the behavior of the cosmic SFR density over the last 7 Gyr is predominantly shaped by non-interacting galaxies.Comment: Accepted for Publication in the Astrophysical Journal. 17 pages of text, 21 figures, 3 tables. Uses emulateapj5.st

Spitzer mid-infrared spectroscopy of compact symmetric objects: What powers radio-loud active galactic nuclei?

We present low- and high-resolution mid-infrared (mid-IR) spectra and photometry for eight compact symmetric objects (CSOs) taken with the Infrared Spectrograph on the Spitzer Space Telescope. The hosts of these young, powerful radio galaxies show significant diversity in their mid-IR spectra. This includes multiple atomic fine-structure lines, H2 gas, polycyclic aromatic hydrocarbon (PAH) emission, warm dust from T = 50 to 150 K, and silicate features in both emission and absorption. There is no evidence in the mid-IR of a single template for CSO hosts, but 5/8 galaxies show similar moderate levels of star formation (<10 M_sun/yr from PAH emission) and silicate dust in a clumpy torus. The total amount of extinction ranges from A_V ~ 10 to 30, and the high-ionization [Ne V] 14.3 and 24.3 um transitions are not detected for any galaxy in the sample. Almost all CSOs show contributions both from star formation and active galactic nuclei (AGNs), suggesting that they occupy a continuum between pure starbursts and AGNs. This is consistent with the hypothesis that radio galaxies are created following a galactic merger; the timing of the radio activity onset means that contributions to the IR luminosity from both merger-induced star formation and the central AGN are likely. Bondi accretion is capable of powering the radio jets for almost all CSOs in the sample; the lack of [Ne V] emission suggests an advection-dominated accretion flow mode as a possible candidate. Merging black holes (BHs) with M_BH > 10^8 M_sun likely exist in all of the CSOs in the sample; however, there is no direct evidence from these data that BH spin energy is being tapped as an alternative mode for powering the radio jets.Comment: 22 pages, 14 figures; published in Ap

The SDSS-III Baryon Oscillation Spectroscopic Survey: Quasar Target Selection for Data Release Nine

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg^2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations in the distribution of Ly-alpha absorption from the spectra of a sample of ~150,000 z>2.2 quasars. Along with measuring the angular diameter distance at z\approx2.5, BOSS will provide the first direct measurement of the expansion rate of the Universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars over 2.2 < z < 3.5, where their colors overlap those of stars. During the first year of the BOSS survey, quasar target selection methods were developed and tested to meet the requirement of delivering at least 15 quasars deg^-2 in this redshift range, out of 40 targets deg^-2. To achieve these surface densities, the magnitude limit of the quasar targets was set at g <= 22.0 or r<=21.85. While detection of the BAO signature in the Ly-alpha absorption in quasar spectra does not require a uniform target selection, many other astrophysical studies do. We therefore defined a uniformly-selected subsample of 20 targets deg^-2, for which the selection efficiency is just over 50%. This "CORE" subsample will be fixed for Years Two through Five of the survey. In this paper we describe the evolution and implementation of the BOSS quasar target selection algorithms during the first two years of BOSS operations. We analyze the spectra obtained during the first year. 11,263 new z>2.2 quasars were spectroscopically confirmed by BOSS. Our current algorithms select an average of 15 z > 2.2 quasars deg^-2 from 40 targets deg^-2 using single-epoch SDSS imaging. Multi-epoch optical data and data at other wavelengths can further improve the efficiency and completeness of BOSS quasar target selection. [Abridged]Comment: 33 pages, 26 figures, 12 tables and a whole bunch of quasars. Submitted to Ap

Community-powered urban stream restoration: A vision for sustainable and resilient urban ecosystems

Urban streams can provide amenities to people living in cities, but those benefits are reduced when streams become degraded, potentially even causing harm (disease, toxic compounds, etc.). Governments and institutions invest resources to improve the values and services provided by urban streams; however, the conception, development, and implementation of such projects may not include meaningful involvement of community members and other stakeholders. Consequently, project objectives may be misaligned with community desires and needs, and projects may fail to achieve their goals. In February 2020, the 5(th) Symposium on Urbanization and Stream Ecology, an interdisciplinary meeting held every 3 to 5 y, met in Austin, Texas, USA, to explore new approaches to urban stream projects, including ways to maximize the full range of potential benefits by better integrating community members into project identification and decision making. The symposium included in-depth discussion about 4 nearby field case studies, participation of multidisciplinary urban stream experts from 5 continents, and input from the Austin community. Institutional barriers to community inclusion were identified and analyzed using real-world examples, both from the case studies and from the literature, which clarified disparities in power, equity, and values. Outcomes of the symposium have been aggregated into a vision that challenges the present institutional approach to urban stream management and a set of strategies to systematically address these barriers to improve restoration solutions. Integrating community members and other stakeholders throughout the urban restoration process, and a transparent decision-making process to resolve divergent objectives, can help identify appropriate goals for realizing both the ecological and social benefits of stream restoration