Anisotropic heating and magnetic field generation due to Raman scattering in laser-plasma interactions

We identify a mechanism for magnetic field generation in the interaction of intense electromagnetic waves and underdense plasmas. We show that Raman scattered plasma waves trap and heat the electrons preferentially in their propagation direction, resulting in a temperature anisotropy. In the trail of laser pulse, we observe magnetic field growth that matches the Weibel mechanism due to the temperature anisotropy. We discuss the role of the initial electron temperature in our results. The predictions are confirmed with multidimensional particle-in-cell simulations. We show how this configuration is an experimental platform to study the long-time evolution of the Weibel instabilityinfo:eu-repo/semantics/publishedVersio

A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets

Extreme Plasma Astrophysics

This is a science white paper submitted to the Astro-2020 and Plasma-2020 Decadal Surveys. The paper describes the present status and emerging opportunities in Extreme Plasma Astrophysics -- a study of astrophysically-relevant plasma processes taking place under extreme conditions that necessitate taking into account relativistic, radiation, and QED effects.Comment: A science white paper submitted to the Astro-2020 and Plasma-2020 Decadal Surveys. 7 pages including cover page and references. Paper updated in late March 2019 to include a several additional co-authors and references, and a few small change

MULTIPLE CURRENT SHEET SYSTEMS IN THE OUTER HELIOSPHERE: ENERGY RELEASE AND TURBULENCE

Accepted for publication in The Astrophysical Journal, March 21, 201

Structural Insights into the Quinolone Resistance Mechanism of Mycobacterium tuberculosis DNA Gyrase

Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA

Structural Basis of Gate-DNA Breakage and Resealing by Type II Topoisomerases

Type II DNA topoisomerases are ubiquitous enzymes with essential functions in DNA replication, recombination and transcription. They change DNA topology by forming a transient covalent cleavage complex with a gate-DNA duplex that allows transport of a second duplex though the gate. Despite its biological importance and targeting by anticancer and antibacterial drugs, cleavage complex formation and reversal is not understood for any type II enzyme. To address the mechanism, we have used X-ray crystallography to study sequential states in the formation and reversal of a DNA cleavage complex by topoisomerase IV from Streptococcus pneumoniae, the bacterial type II enzyme involved in chromosome segregation. A high resolution structure of the complex captured by a novel antibacterial dione reveals two drug molecules intercalated at a cleaved B-form DNA gate and anchored by drug-specific protein contacts. Dione release generated drug-free cleaved and resealed DNA complexes in which the DNA gate instead adopts an unusual A/B-form helical conformation with a Mg2+ ion repositioned to coordinate each scissile phosphodiester group and promote reversible cleavage by active-site tyrosines. These structures, the first for putative reaction intermediates of a type II topoisomerase, suggest how a type II enzyme reseals DNA during its normal reaction cycle and illuminate aspects of drug arrest important for the development of new topoisomerase-targeting therapeutics

A Symmetric Dual Feedback System Provides a Robust and Entrainable Oscillator

Many organisms have evolved molecular clocks to anticipate daily changes in their environment. The molecular mechanisms by which the circadian clock network produces sustained cycles have extensively been studied and transcriptional-translational feedback loops are common structures to many organisms. Although a simple or single feedback loop is sufficient for sustained oscillations, circadian clocks implement multiple, complicated feedback loops. In general, different types of feedback loops are suggested to affect the robustness and entrainment of circadian rhythms

High Confidence Prediction of Essential Genes in Burkholderia Cenocepacia

BACKGROUND: Essential genes are absolutely required for the survival of an organism. The identification of essential genes, besides being one of the most fundamental questions in biology, is also of interest for the emerging science of synthetic biology and for the development of novel antimicrobials. New antimicrobial therapies are desperately needed to treat multidrug-resistant pathogens, such as members of the Burkholderia cepacia complex. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesize that essential genes may be highly conserved within a group of evolutionary closely related organisms. Using a bioinformatics approach we determined that the core genome of the order Burkholderiales consists of 649 genes. All but two of these identified genes were located on chromosome 1 of Burkholderia cenocepacia. Although many of the 649 core genes of Burkholderiales have been shown to be essential in other bacteria, we were also able to identify a number of novel essential genes present mainly, or exclusively, within this order. The essentiality of some of the core genes, including the known essential genes infB, gyrB, ubiB, and valS, as well as the so far uncharacterized genes BCAL1882, BCAL2769, BCAL3142 and BCAL3369 has been confirmed experimentally in B. cenocepacia. CONCLUSIONS/SIGNIFICANCE: We report on the identification of essential genes using a novel bioinformatics strategy and provide bioinformatics and experimental evidence that the large majority of the identified genes are indeed essential. The essential genes identified here may represent valuable targets for the development of novel antimicrobials and their detailed study may shed new light on the functions required to support life