F420H2-Dependent Degradation of Aflatoxin and other Furanocoumarins Is Widespread throughout the Actinomycetales

Two classes of F420-dependent reductases (FDR-A and FDR-B) that can reduce aflatoxins and thereby degrade them have previously been isolated from Mycobacterium smegmatis. One class, the FDR-A enzymes, has up to 100 times more activity than the other. F420 is a cofactor with a low reduction potential that is largely confined to the Actinomycetales and some Archaea and Proteobacteria. We have heterologously expressed ten FDR-A enzymes from diverse Actinomycetales, finding that nine can also use F420H2 to reduce aflatoxin. Thus FDR-As may be responsible for the previously observed degradation of aflatoxin in other Actinomycetales. The one FDR-A enzyme that we found not to reduce aflatoxin belonged to a distinct clade (herein denoted FDR-AA), and our subsequent expression and analysis of seven other FDR-AAs from M. smegmatis found that none could reduce aflatoxin. Certain FDR-A and FDR-B enzymes that could reduce aflatoxin also showed activity with coumarin and three furanocoumarins (angelicin, 8-methoxysporalen and imperatorin), but none of the FDR-AAs tested showed any of these activities. The shared feature of the compounds that were substrates was an α,β-unsaturated lactone moiety. This moiety occurs in a wide variety of otherwise recalcitrant xenobiotics and antibiotics, so the FDR-As and FDR-Bs may have evolved to harness the reducing power of F420 to metabolise such compounds. Mass spectrometry on the products of the FDR-catalyzed reduction of coumarin and the other furanocoumarins shows their spontaneous hydrolysis to multiple products

The diversity of population responses to environmental change

The current extinction and climate change crises pressure us to predict population dynamics with ever‐greater accuracy. Although predictions rest on the well‐advanced theory of age‐structured populations, two key issues remain poorly explored. Specifically, how the age‐dependency in demographic rates and the year‐to‐year interactions between survival and fecundity affect stochastic population growth rates. We use inference, simulations and mathematical derivations to explore how environmental perturbations determine population growth rates for populations with different age‐specific demographic rates and when ages are reduced to stages. We find that stage‐ vs. age‐based models can produce markedly divergent stochastic population growth rates. The differences are most pronounced when there are survival‐fecundity‐trade‐offs, which reduce the variance in the population growth rate. Finally, the expected value and variance of the stochastic growth rates of populations with different age‐specific demographic rates can diverge to the extent that, while some populations may thrive, others will inevitably go extinct

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy.

Peer reviewe

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Additional file 1 of Gait patterns during overground and virtual omnidirectional treadmill walking

Supplementary Material 1: Table S1. Adjusted and unadjusted model estimates of the effects of condition, velocity, leg length, BMI, and sex on forward walking outcomes. Table S2. Adjusted and unadjusted model estimates of the effects of condition, velocity, leg length, BMI, and sex on variabilityoutcomes. Table S3. Adjusted models estimates of the effects of condition, velocity, leg length, BMI, and sex on turn outcome

Molecular Structures of Methyldifluoroarsine, CH₃AsF₂, and Dimethylfluoroarsine, (CH₃)₂AsF, in the Gas Phase As Determined by Electron Diffraction and <i>ab Initio </i>Calculations^†

The structures of gaseous CH3AsF2 and (CH3)2AsF have been determined by electron diffraction incorporating vibrational amplitudes derived from ab initio force fields scaled by experimental frequencies and, for the difluoride, restrained by microwave constants. The following parameters (rα° structure, distances in pm, angles in degrees) have been determined for CH3AsF2:  r(As−C) = 194.6(4), r(As−F) = 173.1(1), ∠CAsF = 95.2(1), ∠FAsF = 97.0(1). For (CH3)2AsF structural refinement gives r(As−C) = 195.1(1), r(As−F) = 175.4(1), ∠CAsF = 95.3(5), and ∠CAsC = 96.9(8). For the series (CH3)3As, (CH3)2AsF, CH3AsF2, and AsF3, both As−C and As−F bond lengths are shortened with increasing numbers of F atoms, but the angles CAsF and FAsF are almost invariant

Colloquium: Proteins: The physics of amorphous evolving matter

Protein is matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with diverse biochemistry. But it is also a point along an evolutionary trajectory determined by the function performed by the protein within a hierarchy of interwoven interaction networks of the cell, the organism, and the population. A physical theory of proteins therefore needs to unify both aspects, the biophysical and the evolutionary. Specifically, it should provide a model of how the DNA gene is mapped into the functional phenotype of the protein. Several physical approaches to the protein problem are reviewed, focusing on a mechanical framework which treats proteins as evolvable condensed matter: Mutations introduce localized perturbations in the gene, which are translated to localized perturbations in the protein matter. A natural tool to examine how mutations shape the phenotype are Green&apos;s functions. They map the evolutionary linkage among mutations in the gene (termed epistasis) to cooperative physical interactions among the amino acids in the protein. The mechanistic view can be applied to examine basic questions of protein evolution and design