Plasmid copy number underlies adaptive mutability in bacteria.

The origin of mutations under selection has been intensively studied using the Cairns-Foster system, in which cells of an Escherichia coli lac mutant are plated on lactose and give rise to 100 Lac+ revertants over several days. These revertants have been attributed variously to stress-induced mutagenesis of nongrowing cells or to selective improvement of preexisting weakly Lac+ cells with no mutagenesis. Most revertant colonies (90%) contain stably Lac+ cells, while others (10%) contain cells with an unstable amplification of the leaky mutant lac allele. Evidence is presented that both stable and unstable Lac+ revertant colonies are initiated by preexisting cells with multiple copies of the F'lac plasmid, which carries the mutant lac allele. The tetracycline analog anhydrotetracycline (AnTc) inhibits growth of cells with multiple copies of the tetA gene. Populations with tetA on their F'lac plasmid include rare cells with an elevated plasmid copy number and multiple copies of both the tetA and lac genes. Pregrowth of such populations with AnTc reduces the number of cells with multiple F'lac copies and consequently the number of Lac+ colonies appearing under selection. Revertant yield is restored rapidly by a few generations of growth without AnTc. We suggest that preexisting cells with multiple F'lac copies divide very little under selection but have enough energy to replicate their F'lac plasmids repeatedly until reversion initiates a stable Lac+ colony. Preexisting cells whose high-copy plasmid includes an internal lac duplication grow under selection and produce an unstable Lac+ colony. In this model, all revertant colonies are initiated by preexisting cells and cannot be stress induced

BL Lacertae Objects and the Extragalactic Gamma-Ray Background

A tight correlation between gamma-ray and radio emission is found for a sample of BL Lacertae (BL Lac) objects detected by Fermi Gamma-ray Space Telescope (Fermi) and the Energetic Gamma-Ray Experiment Telescope (EGRET). The gamma-ray emission of BL Lac objects exhibits strong variability, and the detection rate of gamma-ray BL Lac objects is low, which may be related to the gamma-ray duty cycle of BL Lac objects. We estimate the gamma-ray duty cycle ~ 0.11, for BL Lac objects detected by EGRET and Fermi. Using the empirical relation of gamma-ray emission with radio emission and the estimated gamma-ray duty cycle, we derive the gamma-ray luminosity function (LF) of BL Lac objects from their radio LF. Our derived gamma-ray LF of BL Lac objects can almost reproduce that calculated with the recently released Fermi bright active galactic nuclei (AGN) sample. We find that about 45% of the extragalactic diffuse gamma-ray background (EGRB) is contributed by BL Lac objects. Combining the estimate of the quasar contribution to the EGRB in the previous work, we find that about 77% of the EGRB is contributed by BL Lac objects and radio quasars.Comment: 12 pages, 4 figures, submitte

Intranight optical variability of radio-quiet BL Lacertae objects

Aims: Intranight variation (or microvariation) is a common phenomenon of radio-loud BL Lac objects. However, it is not clear whether the recently found radio-quiet BL Lac objects have the same properties. The occurrence rate of intranight variation is helpful in distinguishing the mechanism of the continuum of radio-quiet BL Lac objects. Methods: We conducted a photometric monitoring of 8 radio-quiet BL Lac objects by the Xinglong 2.16m and Lijiang 2.4m telescopes. The differential light curves are calculated between each target and two comparison stars. To quantify the variation, the significance of variation is examined by a scaled $F$-test. Results: No significant variation is found in the 11 sessions of light curves of 8 radio-quiet BL Lac objects (one galactic source is excluded). The lack of microvariation in radio-quiet BL Lac objects is consistent with the detection rate of microvariation in normal radio-quiet AGNs, but much lower than for radio-loud AGNs. This result indicates that the continua of the radio-quiet BL Lac objects are not dominated by jets that will induce frequent microvariations.Comment: Accepted for publication in Astronomy and Astrophysics; 7 pages, 1 figure, 3 table

Quasi-periodicities of BL Lac Objects

We review the reports of possible year-long quasi-periodicities of BL Lac objects in the $\gamma$-ray and optical bands, and present a homogeneous time analysis of the light curves of PKS2155$-$304, PG1553+113, and BL Lac. Based on results from a survey covering the entire Fermi $\gamma$-ray sky we have estimated the fraction of possible quasi-periodic BL Lac objects. We compared the cyclical behaviour in BL Lac objects with that derived from the search of possible optical periodicities in quasars, and find that at z$\lesssim$1 the cosmic density of quasi-periodic BL Lac objects is larger than that of quasi-periodic quasars. If the BL Lac quasi-periodicities were due to a supermassive binary black hole (SBBH) scenario, there could be a tension with the upper limits on the gravitational wave background measured by the pulsar timing array. The argument clearly indicates the difficulties of generally associating quasi-periodicities of BL Lac objects with SBBHs.Comment: In publication on A&A, 6 pages, 4 figure (11 plots). Minor corrections adde

Polarimetry of optically selected BL Lac candidates from the SDSS

We present and discuss polarimetric observations of 182 targets drawn from an optically selected sample of 240 probable BL Lac candidates out of the SDSS compiled by Collinge et al. (2005). In contrast to most other BL Lac candidate samples extracted from the SDSS, its radio- and/or X-ray properties have not been taken into account for its derivation. Thus, because its selection is based on optical properties alone, it may be less prone to selection effects inherent in other samples derived at different frequencies, so it offers a unique opportunity to extract the first unbiased BL Lac luminosity function that is suitably large in size. We found 124 out of 182 targets (68%) to be polarized, 95 of the polarized targets (77%) to be highly polarized (> 4%). The low-frequency peaked BL Lac candidates in the sample are on average only slightly more polarized than the high-frequency peaked ones. Compared to earlier studies, we found a high duty cycle in high polarization (~66 +2/-14% to be > 4% polarized) in high-frequency peaked BL Lac candidates. This may come from our polarization analysis, which minimizes the contamination by host galaxy light. No evidence of radio-quiet BL Lac objects in the sample was found. Our observations show that the probable sample of BL Lac candidates of Collinge et al. (2005) indeed contains a large number of bona fide BL Lac objects. High S/N spectroscopy and deep X-ray observations are required to construct the first luminosity function of optically selected BL Lac objects and to test more stringently for any radio-quiet BL Lac objects in the sample.Comment: Accepted for publication in A&A. 14 pages, 9 figures, table 1 in electronic form onl

Kinetic approaches to lactose operon induction and bimodality

The quasi-equilibrium approximation is acceptable when molecular interactions are fast enough compared to circuit dynamics, but is no longer allowed when cellular activities are governed by rare events. A typical example is the lactose operon (lac), one of the most famous paradigms of transcription regulation, for which several theories still coexist to describe its behaviors. The lac system is generally analyzed by using equilibrium constants, contradicting single-event hypotheses long suggested by Novick and Weiner (1957). Enzyme induction as an all-or-none phenomenon. Proc. Natl. Acad. Sci. USA 43, 553-566) and recently refined in the study of (Choi et al., 2008. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science 322, 442-446). In the present report, a lac repressor (LacI)-mediated DNA immunoprecipitation experiment reveals that the natural LacI-lac DNA complex built in vivo is extremely tight and long-lived compared to the time scale of lac expression dynamics, which could functionally disconnect the abortive expression bursts and forbid using the standard modes of lac bistability. As alternatives, purely kinetic mechanisms are examined for their capacity to restrict induction through: (i) widely scattered derepression related to the arrival time variance of a predominantly backward asymmetric random walk and (ii) an induction threshold arising in a single window of derepression without recourse to nonlinear multimeric binding and Hill functions. Considering the complete disengagement of the lac repressor from the lac promoter as the probabilistic consequence of a transient stepwise mechanism, is sufficient to explain the sigmoidal lac responses as functions of time and of inducer concentration. This sigmoidal shape can be misleadingly interpreted as a phenomenon of equilibrium cooperativity classically used to explain bistability, but which has been reported to be weak in this system

Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography

Lupus anticoagulants (LAC) consist of anti phospholipid antibodies, detected via their anti coagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n=30) and LAC patient plasma (n=48 non-anticoagulated, n=12 on oral anti coagulants), diluted 1: 1 with a normal plasma pool. The anti-beta(2)-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0-150 mu g/ml). At variance, LAC patient 1: 1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio,and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time,diluted Russell's viper venom time and silica clotting time, measured in 1: 1 plasma mixtures (correlation coefficients 0.59-0.72). The anticoagulant effects of activated protein C (0-7.5 nM) or 23H9 (0-150 mu g/ml), spiked in the 1: 1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence,the normalized thrombin gene ration-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient's treatment with oral anticoagulants

The fraction of BL Lac objects in groups of galaxies

Context: BL Lac objects are a rare class of active galactic nuclei that typically show featureless optical spectra that make it difficult to estimate the redshift. A novel method for estimating the redshift of BL Lac objects has recently been proposed which assumes that these objects typically reside in groups of galaxies. Aims: The aim of this work is to estimate the fraction of BL Lac objects that reside in groups of galaxies. Methods: We use a sample of groups (M12 catalogue) selected by applying a friends-of-friends algorithm in the SDSS DR12. Galaxies in the M12 sample were cross-correlated with the sample of blazars in the BZCAT. Results: We found that 121 galaxies in the M12 catalogue are blazars in the BZCAT sample, all but one are BL Lac objects, and a large fraction are classified as BL Lac-galaxy dominated. Analysing the fraction of galaxies in groups as a function of redshift we have estimated a correction factor that takes into account the typical incompleteness of the catalogues based on the friends-of-friends algorithm. Once this factor was applied to the sample of BL Lac objects with a counterpart in the M12 catalogue, we found that the percentage of BL Lac objects in groups is $\gtrsim 67 \pm 8\%$. Conclusions: The high rate of BL Lac objects in groups found in this work strongly supports a recent method that has successfully estimated the redshift of BL Lac objects with featureless spectra.Comment: Accepted for publication in Astronomy and Astrophysics (Letter