Designing sequential transcription logic: a simple genetic circuit for conditional memory

The ability to learn and respond to recurrent events depends on the capacity to remember transient biological signals received in the past. Moreover, it may be desirable to remember or ignore these transient signals conditioned upon other signals that are active at specific points in time or in unique environments. Here, we propose a simple genetic circuit in bacteria that is capable of conditionally memorizing a signal in the form of a transcription factor concentration. The circuit behaves similarly to a "data latch" in an electronic circuit, i.e. it reads and stores an input signal only when conditioned to do so by a "read command". Our circuit is of the same size as the well-known genetic toggle switch (an unconditional latch) which consists of two mutually repressing genes, but is complemented with a "regulatory front end" involving protein heterodimerization as a simple way to implement conditional control. Deterministic and stochastic analysis of the circuit dynamics indicate that an experimental implementation is feasible based on well-characterized genes and proteins. It is not known, to which extent molecular networks are able to conditionally store information in natural contexts for bacteria. However, our results suggest that such sequential logic elements may be readily implemented by cells through the combination of existing protein-protein interactions and simple transcriptional regulation.Comment: 20 pages, 5 figures; supplementary material available upon request from the author

Measurement of the top quark mass using the matrix element technique in dilepton final states

We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7  fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84  GeV

Characterizing RecA-Independent Induction of Shiga toxin2-Encoding Phages by EDTA Treatment

Background: The bacteriophage life cycle has an important role in Shiga toxin (Stx) expression. The induction of Shiga toxin-encoding phages (Stx phages) increases toxin production as a result of replication of the phage genome, and phage lysis of the host cell also provides a means of Stx toxin to exit the cell. Previous studies suggested that prophage induction might also occur in the absence of SOS response, independently of RecA. Methodology/Principal Findings: The influence of EDTA on RecA-independent Stx2 phage induction was assessed, in laboratory lysogens and in EHEC strains carrying Stx2 phages in their genome, by Real-Time PCR. RecA-independent mechanisms described for phage l induction (RcsA and DsrA) were not involved in Stx2 phage induction. In addition, mutations in the pathway for the stress response of the bacterial envelope to EDTA did not contribute to Stx2 phage induction. The effect of EDTA on Stx phage induction is due to its chelating properties, which was also confirmed by the use of citrate, another chelating agent. Our results indicate that EDTA affects Stx2 phage induction by disruption of the bacterial outer membrane due to chelation of Mg 2+. In all the conditions evaluated, the pH value had a decisive role in Stx2 phage induction. Conclusions/Significance: Chelating agents, such as EDTA and citrate, induce Stx phages, which raises concerns due to their frequent use in food and pharmaceutical products. This study contributes to our understanding of the phenomenon o

Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries

BACKGROUND: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. METHODS AND FINDINGS: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6-2.5). The probability of publication within two years after study completion ranged from 7% to 30%. CONCLUSIONS: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased

Studies of X(3872) and ψ(2S) production in p\bar{p}over-bar collisions at 1.96 TeV

We present various properties of the production of the X (3872) and ψ(2S) states based on 10.4fb‾¹ collected by the D0 experiment in Tevatron p\bar{p} collisions at \sqrt{s} = 1.96 TeV. For both states, we measure the nonprompt fraction fNP of the inclusive production rate due to decays of b-flavored hadrons. We find the fNP values systematically below those obtained at the LHC. The fNP fraction for ψ(2S) increases with transverse momentum, whereas for the X(3872) it is constant within large uncertainties, in agreement with the LHC results. The ratio of prompt to nonprompt ψ(2S) production, (1 - fNP)/fNP, decreases only slightly going from the Tevatron to the LHC, but for the X(3872), this ratio decreases by a factor of about 3. We test the soft-pion signature of the X(3872) modeled as a weakly bound charm-meson pair by studying the production of the X(3872) as a function of the kinetic energy of the X(3872) and the pion in the X(3872) π center-of-mass frame. For a subsample consistent with prompt production, the results are incompatible with a strong enhancement in the production of the X(3872) at the small kinetic energy of the X(3872) and the π in the X(3872)π center-of-mass frame expected for the X + soft-pion production mechanism. For events consistent with being due to decays of hadrons, there is no significant evidence for the soft-pion effect, but its presence at the level expected for the binding energy of 0.17 MeV and the momentum scale Λ = M(π) is not ruled out

Properties of Z±c(3900) produced in pp¯ collisions

We study the production of the exotic charged charmoniumlike state Z ± c ( 3900 ) in p ¯ p collisions through the sequential process ψ ( 4260 ) → Z ± c ( 3900 ) π ∓ , Z ± c ( 3900 ) → J / ψ π ± . Using the subsample of candidates originating from semi-inclusive weak decays of b -flavored hadrons, we measure the invariant mass and natural width to be M = 3902.6 + 5.2 − 5.0 ( stat ) + 3.3 − 1.4 ( syst )     MeV and Γ = 3 2 + 28 − 21 ( stat ) + 26 − 7 ( syst )     MeV , respectively. We search for prompt production of the Z ± c ( 3900 ) through the same sequential process. No significant signal is observed, and we set an upper limit of 0.70 at the 95% credibility level on the ratio of prompt production to the production via b -hadron decays. The study is based on 10.4     f b − 1 of p ¯ p collision data collected by the D0 experiment at the Fermilab Tevatron collider

High-throughput RNA structure probing reveals critical folding events during early 60S ribosome assembly in yeast

While the protein composition of various yeast 60S ribosomal subunit assembly intermediates has been studied in detail, little is known about ribosomal RNA (rRNA) structural rearrangements that take place during early 60S assembly steps. Using a high-throughput RNA structure probing method, we provide nucleotide resolution insights into rRNA structural rearrangements during nucleolar 60S assembly. Our results suggest that many rRNA-folding steps, such as folding of 5.8S rRNA, occur at a very specific stage of assembly, and propose that downstream nuclear assembly events can only continue once 5.8S folding has been completed. Our maps of nucleotide flexibility enable making predictions about the establishment of protein-rRNA interactions, providing intriguing insights into the temporal order of protein-rRNA as well as long-range inter-domain rRNA interactions. These data argue that many distant domains in the rRNA can assemble simultaneously during early 60S assembly and underscore the enormous complexity of 60S synthesis.Ribosome biogenesis is a dynamic process that involves the ordered assembly of ribosomal proteins and numerous RNA structural rearrangements. Here the authors apply ChemModSeq, a high-throughput RNA structure probing method, to quantitatively measure changes in RNA flexibility during the nucleolar stages of 60S assembly in yeast

Recent advances in studies of polymicrobial interactions in oral biofilms

The oral cavity supports a complex and finely balanced consortium of microbial species, many of which cooperate within structured biofilms. These communities develop through multitudinous synergistic and antagonistic interspecies relationships. Changes in the dynamics of oral microbial populations are associated with the transition from healthy teeth and gums to dental caries, gingivitis and periodontitis. Understanding the ecology of oral biofilm communities, and how different species communicate within a given host, will inform new strategies for treatment and prevention of oral diseases. Advances in sequencing technologies have fuelled an increasing trend towards global genomic and proteomic approaches to determine the key factors that initiate oral diseases. Whilst metabolic profiling seeks to identify phenotypic changes of whole microbial communities, transcriptomic studies are exploring their complex interactions with each other and the host. This review discusses the most recent in vitro and in vivo studies of interspecies interactions within polymicrobial oral biofilms

Combination of D0 measurements of the top quark mass

We present a combination of measurements of the top quark mass by the D0 experiment in the lepton+jets and dilepton channels. We use all the data collected in Run I (1992–1996) at √s=1.8  TeV and Run II (2001–2011) at √s=1.96  TeV of the Tevatron p¯p collider, corresponding to integrated luminosities of 0.1  fb−1 and 9.7  fb−1, respectively. The combined result is: mt=174.95±0.40(stat)±0.64(syst)  GeV=174.95±0.75  GeV