YoeB toxin is activated during thermal stress.

Type II toxin-antitoxin (TA) modules are thought to mediate stress-responses by temporarily suppressing protein synthesis while cells redirect transcription to adapt to environmental change. Here, we show that YoeB, a ribosome-dependent mRNase toxin, is activated in Escherichia coli cells grown at elevated temperatures. YoeB activation is dependent on Lon protease, suggesting that thermal stress promotes increased degradation of the YefM antitoxin. Though YefM is efficiently degraded in response to Lon overproduction, we find that Lon antigen levels do not increase during heat shock, indicating that another mechanism accounts for temperature-induced YefM proteolysis. These observations suggest that YefM/YoeB functions in adaptation to temperature stress. However, this response is distinct from previously described models of TA function. First, YoeB mRNase activity is maintained over several hours of culture at 42°C, indicating that thermal activation is not transient. Moreover, heat-activated YoeB does not induce growth arrest nor does it suppress global protein synthesis. In fact, E. coli cells proliferate more rapidly at elevated temperatures and instantaneously accelerate their growth rate in response to acute heat shock. We propose that heat-activated YoeB may serve a quality control function, facilitating the recycling of stalled translation complexes through ribosome rescue pathways

Connections Between Local and Global Turbulence in Accretion Disks

We analyze a suite of global magnetohydrodynamic (MHD) accretion disk simulations in order to determine whether scaling laws for turbulence driven by the magnetorotational instability, discovered via local shearing box studies, are globally robust. The simulations model geometrically-thin disks with zero net magnetic flux and no explicit resistivity or viscosity. We show that the local Maxwell stress is correlated with the self-generated local vertical magnetic field in a manner that is similar to that found in local simulations. Moreover, local patches of vertical field are strong enough to stimulate and control the strength of angular momentum transport across much of the disk. We demonstrate the importance of magnetic linkages (through the low-density corona) between different regions of the disk in determining the local field, and suggest a new convergence requirement for global simulations -- the vertical extent of the corona must be fully captured and resolved. Finally, we examine the temporal convergence of the average stress, and show that an initial long-term secular drift in the local flux-stress relation dies away on a time scale that is consistent with turbulent mixing of the initial magnetic field.Comment: 8 Pages, 7 Figures ApJ, In Pres

Functional plasticity of antibacterial EndoU toxins.

Bacteria use several different secretion systems to deliver toxic EndoU ribonucleases into neighboring cells. Here, we present the first structure of a prokaryotic EndoU toxin in complex with its cognate immunity protein. The contact-dependent growth inhibition toxin CdiA-CTSTECO31 from Escherichia coli STEC_O31 adopts the eukaryotic EndoU fold and shares greatest structural homology with the nuclease domain of coronavirus Nsp15. The toxin contains a canonical His-His-Lys catalytic triad in the same arrangement as eukaryotic EndoU domains, but lacks the uridylate-specific ribonuclease activity that characterizes the superfamily. Comparative sequence analysis indicates that bacterial EndoU domains segregate into at least three major clades based on structural variations in the N-terminal subdomain. Representative EndoU nucleases from clades I and II degrade tRNA molecules with little specificity. In contrast, CdiA-CTSTECO31 and other clade III toxins are specific anticodon nucleases that cleave tRNAGlu between nucleotides C37 and m2 A38. These findings suggest that the EndoU fold is a versatile scaffold for the evolution of novel substrate specificities. Such functional plasticity may account for the widespread use of EndoU effectors by diverse inter-bacterial toxin delivery systems

BlackOPs: Increasing confidence in variant detection through mappability filtering

Identifying variants using high-throughput sequen-cing data is currently a challenge because true biological variants can be indistinguishable from technical artifacts. One source of technical arti-fact results from incorrectly aligning experimen-tally observed sequences to their true genomic origin (‘mismapping’) and inferring differences in mismapped sequences to be true variants. We de-veloped BlackOPs, an open-source tool that simu-lates experimental RNA-seq and DNA whole exome sequences derived from the reference genome, aligns these sequences by custom parameters, detects variants and outputs a blacklist of positions and alleles caused by mismapping. Blacklist

SigFuge: Single gene clustering of RNA-seq reveals differential isoform usage among cancer samples

High-throughput sequencing technologies, including RNA-seq, have made it possible to move beyond gene expression analysis to study transcriptional events including alternative splicing and gene fusions. Furthermore, recent studies in cancer have suggested the importance of identifying transcriptionally altered loci as biomarkers for improved prognosis and therapy. While many statistical methods have been proposed for identifying novel transcriptional events with RNA-seq, nearly all rely on contrasting known classes of samples, such as tumor and normal. Few tools exist for the unsupervised discovery of such events without class labels. In this paper, we present SigFuge for identifying genomic loci exhibiting differential transcription patterns across many RNA-seq samples. SigFuge combines clustering with hypothesis testing to identify genes exhibiting alternative splicing, or differences in isoform expression. We apply SigFuge to RNA-seq cohorts of 177 lung and 279 head and neck squamous cell carcinoma samples from the Cancer Genome Atlas, and identify several cases of differential isoform usage including CDKN2A, a tumor suppressor gene known to be inactivated in a majority of lung squamous cell tumors. By not restricting attention to known sample stratifications, SigFuge offers a novel approach to unsupervised screening of genetic loci across RNA-seq cohorts. SigFuge is available as an R package through Bioconductor

Low-Frequency Oscillations in Global Simulations of Black Hole Accretion

We have identified the presence of large-scale, low-frequency dynamo cycles in a long-duration, global, magnetohydrodynamic (MHD) simulation of black hole accretion. Such cycles had been seen previously in local shearing box simulations, but we discuss their evolution over 1,500 inner disk orbits of a global pi/4 disk wedge spanning two orders of magnitude in radius and seven scale heights in elevation above/below the disk midplane. The observed cycles manifest themselves as oscillations in azimuthal magnetic field occupying a region that extends into a low-density corona several scale heights above the disk. The cycle frequencies are ten to twenty times lower than the local orbital frequency, making them potentially interesting sources of low-frequency variability when scaled to real astrophysical systems. Furthermore, power spectra derived from the full time series reveal that the cycles manifest themselves at discrete, narrow-band frequencies that often share power across broad radial ranges. We explore possible connections between these simulated cycles and observed low-frequency quasi-periodic oscillations (LFQPOs) in galactic black hole binary systems, finding that dynamo cycles have the appropriate frequencies and are located in a spatial region associated with X-ray emission in real systems. Derived observational proxies, however, fail to feature peaks with RMS amplitudes comparable to LFQPO observations, suggesting that further theoretical work and more sophisticated simulations will be required to form a complete theory of dynamo-driven LFQPOs. Nonetheless, this work clearly illustrates that global MHD dynamos exhibit quasi-periodic behavior on timescales much longer than those derived from test particle considerations.Comment: Version accepted to The Astrophysical Journal, 8 pages, 7 figure