Diversity in lac Operon Regulation among Diverse Escherichia coli Isolates Depends on the Broader Genetic Background but Is Not Explained by Genetic Relatedness

This work is licensed under a Creative Commons Attribution 4.0 International License.Transcription of bacterial genes is controlled by the coordinated action of cis- and trans-acting regulators. The activity and mode of action of these regulators can reflect different requirements for gene products in different environments. A well-studied example is the regulatory function that integrates the environmental availability of glucose and lactose to control the Escherichia coli lac operon. Most studies of lac operon regulation have focused on a few closely related strains. To determine the range of natural variation in lac regulatory function, we introduced a reporter construct into 23 diverse E. coli strains and measured expression with combinations of inducer concentrations. We found a wide range of regulatory functions. Several functions were similar to the one observed in a reference lab strain, whereas others depended weakly on the presence of cAMP. Some characteristics of the regulatory function were explained by the genetic relatedness of strains, indicating that differences varied on relatively short time scales. The regulatory characteristics explained by genetic relatedness were among those that best predicted the initial growth of strains following transition to a lactose environment, suggesting a role for selection. Finally, we transferred the lac operon, with the lacI regulatory gene, from five natural isolate strains into a reference lab strain. The regulatory function of these hybrid strains revealed the effect of local and global regulatory elements in controlling expression. Together, this work demonstrates that regulatory functions can be varied within a species and that there is variation within a species to best match a function to particular environments

The Far Ultraviolet Spectroscopic Explorer Survey of OVI Absorption in the Disk of the Milky Way

To probe the distribution and physical characteristics of interstellar gas at temperatures T ~ 3e5 K in the disk of the Milky Way, we have used the Far Ultraviolet Spectroscopic Explorer (FUSE) to observe absorption lines of OVI toward 148 early-type stars situated at distances 1 kpc. After subtracting off a mild excess of OVI arising from the Local Bubble, combining our new results with earlier surveys of OVI, and eliminating stars that show conspicuous localized X-ray emission, we find an average OVI mid-plane density n_0 = 1.3e-8 cm^-3. The density decreases away from the plane of the Galaxy in a way that is consistent with an exponential scale height of 3.2 kpc at negative latitudes or 4.6 kpc at positive latitudes. Average volume densities of OVI along different sight lines exhibit a dispersion of about 0.26 dex, irrespective of the distances to the target stars. This indicates that OVI does not arise in randomly situated clouds of a fixed size and density, but instead is distributed in regions that have a very broad range of column densities, with the more strongly absorbing clouds having a lower space density. Line widths and centroid velocities are much larger than those expected from differential Galactic rotation, but they are nevertheless correlated with distance and N(OVI), which reinforces our picture of a diverse population of hot plasma regions that are ubiquitous over the entire Galactic disk. The velocity extremes of the OVI profiles show a loose correlation with those of very strong lines of less ionized species, supporting a picture of a turbulent, multiphase medium churned by shock-heated gas from multiple supernova explosions.Comment: Accepted for publication in ApJS. Preprint with full resolution images and all 148 spectra available at http://www.astro.princeton.edu/~dvb/o

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Estrogen receptor β exerts tumor suppressive effects in prostate cancer through repression of androgen receptor activity.

Estrogen receptor β (ERβ) was first identified in the rodent prostate and is abundantly expressed in human and rodent prostate epithelium, stroma, immune cells and endothelium of the blood vessels. In the prostates of mice with inactivated ERβ, mutant phenotypes include epithelial hyperplasia and increased expression of androgen receptor (AR)-regulated genes, most of which are also upregulated in prostate cancer (PCa). ERβ is expressed in both basal and luminal cells in the prostate while AR is expressed in luminal but not in the basal cell layer which harbors the prostate stem cells. To investigate the mechanisms of action of ERβ and its potential cross-talk with AR, we used RNA-seq to study the effects of estradiol or the synthetic ligand, LY3201, in AR-positive LNCaP PCa cells which had been engineered to express ERβ. Transcriptomic analysis indicated relatively few changes in gene expression with ERβ overexpression, but robust responses following ligand treatments. There is significant overlap of responsive genes between the two ligands, estradiol and LY3201 as well as ligand-specific alterations. Gene set analysis of down-regulated genes identified an enrichment of androgen-responsive genes, such as FKBP5, CAMKK2, and TBC1D4. Consistently, AR transcript, protein levels, and transcriptional activity were down-regulated following ERβ activation. In agreement with this, we find that the phosphorylation of the CAMKK2 target, AMPK, was repressed by ligand-activated ERβ. These findings suggest that ERβ-mediated signaling pathways are involved in the negative regulation of AR expression and activity, thus supporting a tumor suppressive role for ERβ in PCa