MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale.

A considerable proportion of mammalian gene expression undergoes circadian oscillations. Post-transcriptional mechanisms likely make important contributions to mRNA abundance rhythms. We have investigated how microRNAs (miRNAs) contribute to core clock and clock-controlled gene expression using mice in which miRNA biogenesis can be inactivated in the liver. While the hepatic core clock was surprisingly resilient to miRNA loss, whole transcriptome sequencing uncovered widespread effects on clock output gene expression. Cyclic transcription paired with miRNA-mediated regulation was thus identified as a frequent phenomenon that affected up to 30% of the rhythmic transcriptome and served to post-transcriptionally adjust the phases and amplitudes of rhythmic mRNA accumulation. However, only few mRNA rhythms were actually generated by miRNAs. Overall, our study suggests that miRNAs function to adapt clock-driven gene expression to tissue-specific requirements. Finally, we pinpoint several miRNAs predicted to act as modulators of rhythmic transcripts, and identify rhythmic pathways particularly prone to miRNA regulation.DOI: http://dx.doi.org/10.7554/eLife.02510.001

Transcriptome-wide sites of collided ribosomes reveal principles of translational pausing.

Translation initiation is the major regulatory step defining the rate of protein production from an mRNA. Meanwhile, the impact of nonuniform ribosomal elongation rates is largely unknown. Using a modified ribosome profiling protocol based on footprints from two closely packed ribosomes (disomes), we have mapped ribosomal collisions transcriptome-wide in mouse liver. We uncover that the stacking of an elongating onto a paused ribosome occurs frequently and scales with translation rate, trapping ∼10% of translating ribosomes in the disome state. A distinct class of pause sites is indicative of deterministic pausing signals. Pause site association with specific amino acids, peptide motifs, and nascent polypeptide structure is suggestive of programmed pausing as a widespread mechanism associated with protein folding. Evolutionary conservation at disome sites indicates functional relevance of translational pausing. Collectively, our disome profiling approach allows unique insights into gene regulation occurring at the step of translation elongation

Effective damping in the Raman cooling of trapped ions

We present a method of treating the interaction of a single three-level ion with two laser beams. The idea is to apply a unitary transformation such that the exact transformed Hamiltonian has one of the three levels decoupled for all values of the detunings. When one takes into account damping, the evolution of the system is governed by a master equation usually obtained via adiabatic approximation under the assumption of far-detuned lasers. To go around the drawbacks of this technique, we use the same unitary transformation to get an effective master equation.Comment: 15 pages, 5 figures. To appear in Optics Communication

Profiling for run-time checking of computational properties and performance debugging in logic programs

Although several profiling techniques for identifying performance bottlenecks in logic programs have been developed, they are generally not automatic and in most cases they do not provide enough information for identifying the root causes of such bottlenecks. This complicates using their results for guiding performance improvement. We present a profiling method and tool that provides such explanations. Our profiler associates cost centers to certain program elements and can measure different types of resource-related properties that affect performance, preserving the precedence of cost centers in the cali graph. It includes an automatic method for detecting procedures that are performance bottlenecks. The profiling tool has been integrated in a previously developed run-time checking framework to allow verification of certain properties when they cannot be verified statically. The approach allows checking global computational properties which require complex instrumentation tracking information about previous execution states, such as, e.g., that the execution time accumulated by a given procedure is not greater than a given bound. We have built a prototype implementation, integrated it in the Ciao/CiaoPP system and successfully applied it to performance improvement, automatic optimization (e.g., resource-aware specialization of programs), run-time checking, and debugging of global computational properties (e.g., resource usage) in Prolog programs

Mimicking a Kerrlike medium in the dispersive regime of second-harmonic generation

We find an effective Hamiltonian describing the process of second-harmonic generation in the far-off resonant limit. We show that the dynamics of the fundamental mode is governed by a Kerrlike Hamiltonian. Some dynamical consequences are examined.Comment: 12 pages, 4 figures Submitted to Optics Communication

Gradient models of the axion-photon coupling

We establish an extended version of the Einstein - Maxwell - axion model by introducing into the Lagrangian cross-terms, which contain the gradient four-vector of the pseudoscalar (axion) field in convolution with the Maxwell tensor. The gradient model of the axion-photon coupling is applied to cosmology: we analyze the Bianchi-I type Universe with an initial magnetic field, electric field induced by the axion-photon interaction, cosmological constant and dark matter, which is described in terms of the pseudoscalar (axion) field. Analytical, qualitative and numerical results are presented in detail for two distinguished epochs: first, for the early Universe with magnetic field domination; second, for the stage of late-time accelerated expansion.Comment: 26 pages, 5 figures, accepted for publication in The European Physical Journal

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity

Acknowledgements This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01- 0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (SFRH/BD/136814/2018 to S.M.G., SFRH/BD/141127/2018 to C.D.O., PD/BD/137680/2018 to D.A., IF/00474/2014 to N.S.O., IF/01390/2014 to E.T., IF/00959/2014 to S.C., IF/00021/2014 to R.S., PTDC/SAU-SER/29635/2017 and CEECIND/04601/2017 to C.C., and CEECIND/03628/2017 to A.C.), the Institut Mérieux (Mérieux Research Grant 2017 to C.C.), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2017 to A.C.). M.G.N. was supported by a Spinoza grant of the Netherlands Organization for Scientific Research. A.A.B. was supported by the Deutsche Forschungsgemeinschaft Collaborative Research Center/Transregio TR124 FungiNet (project A1). G.D.B. was funded by the Wellcome Trust (102705), the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPublisher PD

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters