The stringent response inhibits 70S ribosome formation in Staphylococcus aureus by impeding GTPase-ribosome interactions

During nutrient limitation, bacteria produce the alarmones (p)ppGpp as effectors of a stress signaling network termed the stringent response. RsgA, RbgA, Era, and HflX are four ribosome-associated GTPases (RA-GTPases) that bind to (p)ppGpp in Staphylococcus aureus. These enzymes are cofactors in ribosome assembly, where they cycle between the ON (GTP-bound) and OFF (GDP-bound) ribosome-associated states. Entry into the OFF state occurs upon hydrolysis of GTP, with GTPase activity increasing substantially upon ribosome association. When bound to (p)ppGpp, GTPase activity is inhibited, reducing 70S ribosome assembly and growth. Here, we determine how (p)ppGpp impacts RA-GTPase-ribosome interactions. We show that RA-GTPases preferentially bind to 59-diphosphate-containing nucleotides GDP and ppGpp over GTP, which is likely exploited as a regulatory mechanism within the cell to shut down ribosome biogenesis during stress. Stopped-flow fluorescence and association assays reveal that when bound to (p)ppGpp, the association of RA-GTPases to ribosomal subunits is destabilized, both in vitro and within bacterial cells. Consistently, structural analysis of the ppGpp-bound RA-GTPase RsgA reveals an OFF-state conformation similar to the GDP-bound state, with the G2/switch I loop adopting a conformation incompatible with ribosome association. Altogether, we highlight (p)ppGpp-mediated inhibition of RA-GTPases as a major mechanism of stringent response-mediated ribosome assembly and growth control

Lofar low-band antenna observations of the 3C 295 and boötes fields : Source counts and ultra-steep spectrum sources

© 2018 The American Astronomical Society. All rights reserved.We present Low Frequency Array (LOFAR) Low Band observations of the Boötes and 3C 295 fields. Our images made at 34, 46, and 62 MHz reach noise levels of 12, 8, and 5 mJy beam-1, making them the deepest images ever obtained in this frequency range. In total, we detect between 300 and 400 sources in each of these images, covering an area of 17-52 deg2. From the observations, we derive Euclidean-normalized differential source counts. The 62 MHz source counts agree with previous GMRT 153 MHz and Very Large Array 74 MHz differential source counts, scaling with a spectral index of -0.7. We find that a spectral index scaling of -0.5 is required to match up the LOFAR 34 MHz source counts. This result is also in agreement with source counts from the 38 MHz 8C survey, indicating that the average spectral index of radio sources flattens toward lower frequencies. We also find evidence for spectral flattening using the individual flux measurements of sources between 34 and 1400 MHz and by calculating the spectral index averaged over the source population. To select ultra-steep spectrum (α < -1.1) radio sources that could be associated with massive high-redshift radio galaxies, we compute spectral indices between 62 MHz, 153 MHz, and 1.4 GHz for sources in the Boötes field. We cross-correlate these radio sources with optical and infrared catalogs and fit the spectral energy distribution to obtain photometric redshifts. We find that most of these ultra-steep spectrum sources are located in the 0.7 ≲ z ≲ 2.5 range.Peer reviewe

GW190814: gravitational waves from the coalescence of a 23 solar mass black hole with a 2.6 solar mass compact object

We report the observation of a compact binary coalescence involving a 22.2–24.3 Me black hole and a compact object with a mass of 2.50–2.67 Me (all measurements quoted at the 90% credible level). The gravitational-wave signal, GW190814, was observed during LIGO’s and Virgo’s third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to 18.5 deg2 at a distance of - + 241 45 41 Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves, - + 0.112 0.009 0.008, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to �0.07. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries

A study of repeated DNA sequences in the orthopteran Stauroderus scalaris

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN1789 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Molecular genetic analysis of enoyl-acyl carrier protein reductase inhibition by diazarborine.

Diazaborine and isoniazid are, at first sight, unrelated anti-bacterial agents that inhibit the enoyl-ACP reductase (ENR) of Escherichia coli and Mycobacterium tuberculosis respectively. The crystal structures of these enzymes including that of the diazaborine-inhibited E. coli ENR have been obtained at high resolution. Site-directed mutagenesis was used to study the importance of amino acid residues in diazaborine susceptibility and enzyme function. The results show that drug binding and inhibition require the presence of a glycine residue at position 93 of E. coli ENR or at the structurally equivalent position in the plant homologue, which is naturally resistant to the drug. The data confirm the hypothesis that any amino acid side-chain other than hydrogen at this position within the three-dimensional structure of these enzymes will affect diazaborine resistance by encroaching into the drug binding site. Substitutions of Gly-93 by amino acids with small side-chains, such as serine, alanine, cysteine and valine, hardly affected the catalytic parameters and rendered the bacterial host resistant to the drug, larger amino acid side-chains, such as that of arginine, histidine, lysine acid glutamine, completely inactivated the activity of the enzyme