Communication between levels of transcriptional control improves robustness and adaptivity

Regulation of eukaryotic gene expression depends on groups of related proteins acting at the levels of chromatin organization, transcriptional initiation, RNA processing, and nuclear transport. However, a unified understanding of how these different levels of transcriptional control interact has been lacking. Here, we combine genome-wide protein–DNA binding data from multiple sources to infer the connections between functional groups of regulators in Saccharomyces cerevisiae. Our resulting transcriptional network uncovers novel biological relationships; supporting experiments confirm new associations between actively transcribed genes and Sir2 and Esc1, two proteins normally linked to silencing chromatin. Analysis of the regulatory network also reveals an elegant architecture for transcriptional control. Using communication theory, we show that most protein regulators prefer to form modules within their functional class, whereas essential proteins maintain the sparse connections between different classes. Moreover, we provide evidence that communication between different regulatory groups improves the robustness and adaptivity of the cell

A Src inhibitor regulates the cell cycle of human pluripotent stem cells and improves directed differentiation

Driving human pluripotent stem cells (hPSCs) into specific lineages is an inefficient and challenging process. We show that a potent Src inhibitor, PP1, regulates expression of genes involved in the G1 to S phase transition of the cell cycle, activates proteins in the retinoblastoma family, and subsequently increases the differentiation propensities of hPSCs into all three germ layers. We further demonstrate that genetic suppression of Src regulates the activity of the retinoblastoma protein and enhances the differentiation potential of hPSCs across all germ layers. These positive effects extend beyond the initial germ layer specification and enable efficient differentiation at subsequent stages of differentiation

Genetic diversity and host alternation of the egg parasitoid Oencyrtus pityocampae between the pine processionary moth and caper bug

Research ArticleThe increased use of molecular tools for species identification in recent decades revealed that each of many apparently generalist parasitoids are actually a complex of morphologically similar congeners, most of which have a rather narrow host range. Ooencyrtus pityocampae (OP), an important egg parasitoid of the pine processionary moth (PPM), is considered a generalist parasitoid. OP emerges from PPM eggs after winter hibernation, mainly in spring and early summer, long before the eggs of the next PPM generation occurs. The occurrence of OP in eggs of the variegated caper bug (CB) Stenozygum coloratum in spring and summer suggests that OP populations alternate seasonally between PPM and CB. However, the identity of OP population on CB eggs seemed uncertain; unlike OP-PPM populations, the former displayed apparently high male/female ratios and lack of attraction to the PPM sex pheromone. We studied the molecular identities of the two populations since the morphological identification of the genus Ooencyrtus, and OP in particular, is difficult. Sequencing of COI and ITS2 DNA fragments and AFLP analysis of individuals from both hosts revealed no apparent differences between the OP-PPM and the OP-CB populations for both the Israeli and the Turkish OPs, which therefore supported the possibility of host alternation. Sequencing data extended our knowledge of the genetic structure of OP populations in the Mediterranean area, and revealed clear separation between East and West Mediterranean populations. The overall level of genetic diversity was rather small, with the Israeli population much less diverse than all others; possible explanations for this finding are discussed. The findings support the possibility of utilizing the CB and other hosts for enhancing biological control of the PPMinfo:eu-repo/semantics/publishedVersio

Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression

Maintenance of pluripotency and specification towards a new cell fate are both dependent on precise interactions between extrinsic signals and transcriptional and epigenetic regulators. Directed methylation of cytosines by the de novo methyltransferases DNMT3A and DNMT3B plays an important role in facilitating proper differentiation, whereas DNMT1 is essential for maintaining global methylation levels in all cell types. Here, we generated single-cell mRNA expression data from wild-type, DNMT3A, DNMT3A/3B and DNMT1 knockout human embryonic stem cells and observed a widespread increase in cellular and transcriptional variability, even with limited changes in global methylation levels in the de novo knockouts. Furthermore, we found unexpected transcriptional repression upon either loss of the de novo methyltransferase DNMT3A or the double knockout of DNMT3A/3B that is further propagated upon differentiation to mesoderm and ectoderm. Taken together, our single-cell RNA-sequencing data provide a high-resolution view into the consequences of depleting the three catalytically active DNMTs in human pluripotent stem cells

Ultraweak excitations of the quantum vacuum as physical models of gravity

It has been argued by several authors that the space-time curvature observed in gravitational fields, and the same idea of forms of physical equivalence different from the Lorentz group, might emerge from the dynamical properties of the physical flat-space vacuum in a suitable hydrodynamic limit. To explore this idea, one could start by representing the physical vacuum as a Bose condensate of elementary quanta and look for vacuum excitations that, on a coarse grained scale, resemble the Newtonian potential. In this way, it is relatively easy to match the weak-field limit of classical General Relativity or of some of its possible variants. The idea that Bose condensates can provide various forms of gravitational dynamics is not new. Here, I want to emphasize some genuine quantum field theoretical aspects that can help to understand i) why infinitesimally weak, 1/r interactions can indeed arise from the same physical vacuum of electroweak and strong interactions and ii) why, on a coarse-grained scale, their dynamical effects can be re-absorbed into an effective curved metric structure.Comment: 30 pages, no figures, accepted by Classical and Quantum Gravit

The PADME electromagnetic calorimeter

The PADME experiment, hosted at Laboratori Nazionali di Frascati in Italy, is going to start its data taking in September 2018. It is designed to search for the Dark Photon (indicated by the symbol A′), an hypothetical particle that can explain the Dark Matter elusiveness, possibly produced in the reaction e + e - → A′ γ. Together with the target, the segmented electromagnetic calorimeter is the most important component of the experiment, since it is needed to detect the recoil photon energy and position, in such a way to measure the A′ mass. It will consist of 616 2.1 × 2.1 × 23.0 cm3 BGO crystals arranged in a cylindrical shape and read by HZC photomultipliers with a diameter of 1.9 cm. Here we present the results obtained during the measurements performed on the scintillating units with a radioactive source and test beams, together with an overall description of the entire experiment

Generic representations of abelian groups and extreme amenability

If $G$ is a Polish group and $\Gamma$ is a countable group, denote by \Hom(\Gamma, G) the space of all homomorphisms $\Gamma \to G$. We study properties of the group \cl{\pi(\Gamma)} for the generic \pi \in \Hom(\Gamma, G), when $\Gamma$ is abelian and $G$ is one of the following three groups: the unitary group of an infinite-dimensional Hilbert space, the automorphism group of a standard probability space, and the isometry group of the Urysohn metric space. Under mild assumptions on $\Gamma$, we prove that in the first case, there is (up to isomorphism of topological groups) a unique generic \cl{\pi(\Gamma)}; in the other two, we show that the generic \cl{\pi(\Gamma)} is extremely amenable. We also show that if $\Gamma$ is torsion-free, the centralizer of the generic $\pi$ is as small as possible, extending a result of King from ergodic theory.Comment: Version

Commissioning of the PADME experiment with a positron beam

The PADME experiment is designed to search for a hypothetical dark photon A' produced in positron-electron annihilation using a bunched positron beam at the Beam Test Facility of the INFN Laboratori Nazionali di Frascati. The expected sensitivity to the A'-photon mixing parameter ϵ is 10-3, for A' mass ≤ 23.5 MeV/c 2 after collecting ∼1013 positrons-on-target. This paper presents the PADME detector status after commissioning in July 2019. In addition, the software algorithms employed to reconstruct physics objects, such as photons and charged particles, and the calibration procedures adopted are illustrated in detail. The results show that the experimental apparatus reaches the design performance, and is able to identify and measure standard electromagnetic processes, such as positron bremsstrahlung and electron-positron annihilation into two photons

Stochastic and Regulatory Role of Chromatin Silencing in Genomic Response to Environmental Changes

Phenotypic diversity and fidelity can be balanced by controlling stochastic molecular mechanisms. Epigenetic silencing is one that has a critical role in stress response. Here we show that in yeast, incomplete silencing increases stochastic noise in gene expression, probably owing to unstable chromatin structure. Telomere position effect is suggested as one mechanism. Expression diversity in a population achieved in this way may render a subset of cells to readily respond to various acute stresses. By contrast, strong silencing tends to suppress noisy expression of genes, in particular those involved in life cycle control. In this regime, chromatin may act as a noise filter for precisely regulated responses to environmental signals that induce huge phenotypic changes such as a cell fate transition. These results propose modulation of chromatin stability as an important determinant of environmental adaptation and cellular differentiation

Characterisation and performance of the PADME electromagnetic calorimeter

The PADME experiment at the LNF Beam Test Facility searches for dark photons produced in the annihilation of positrons with the electrons of a fixed target. The strategy is to look for the reaction e+ + e− → γ + A0, where A0 is the dark photon, which cannot be observed directly or via its decay products. The electromagnetic calorimeter plays a key role in the experiment by measuring the energy and position of the final-state γ. The missing four-momentum carried away by the A0 can be evaluated from this information and the particle mass inferred. This paper presents the design, construction, and calibration of the PADME’s electromagnetic calorimeter. The results achieved in terms of equalisation, detection efficiency and energy resolution during the first phase of the experiment demonstrate the effectiveness of the various tools used to improve the calorimeter performance with respect to earlier prototypes