Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450_(BM3) demethylases

Polysaccharides comprise an extremely important class of biopolymers that play critical roles in a wide range of biological processes, but the synthesis of these compounds is challenging because of their complex structures. We have developed a chemoenzymatic method for regioselective deprotection of monosaccharide substrates using engineered Bacillus megaterium cytochrome P450 (P450_(BM3)) demethylases that provides a highly efficient means to access valuable intermediates, which can be converted to a wide range of substituted monosaccharides and polysaccharides. Demethylases displaying high levels of regioselectivity toward a number of protected monosaccharides were identified using a combination of protein and substrate engineering, suggesting that this approach ultimately could be used in the synthesis of a wide range of substituted mono- and polysaccharides for studies in chemistry, biology, and medicine

Proteogenomic analysis of Georgfuchsia toluolica revealed unexpected concurrent aerobic and anaerobic toluene degradation

Denitrifying Betaproteobacteria play a key role in the anaerobic degradation of monoaromatic hydrocarbons. We performed a multi-omics study to better understand the metabolism of the representative organism Georgfuchsia toluolica strain G5G6 known as a strict anaerobe coupling toluene oxidation with dissimilatory nitrate and Fe(III) reduction. Despite the genomic potential for degradation of different carbon sources, we did not find sugar or organic acid transporters, in line with the inability of strain G5G6 to use these substrates. Using a proteomics analysis, we detected proteins of fumarate-dependent toluene activation, membrane-bound nitrate reductase, and key components of the metal-reducing (Mtr) pathway under both nitrate- and Fe(III)-reducing conditions. High abundance of the multiheme cytochrome MtrC implied that a porincytochrome complex was used for respiratory Fe(III) reduction. Remarkably, strain G5G6 contains a full set of genes for aerobic toluene degradation, and we detected enzymes of aerobic toluene degradation under both nitrate- and Fe(III)-reducing conditions. We further detected an ATP-dependent benzoyl-CoA reductase, reactive oxygen species detoxification proteins, and cytochrome c oxidase indicating a facultative anaerobic lifestyle of strain G5G6. Correspondingly, we found diffusion through the septa a substantial source of oxygen in the cultures enabling concurrent aerobic and anaerobic toluene degradation by strain G5G6.This work was supported by Wageningen University & Research through its investment theme Resilience, the Technology Foundation (STW), the Applied Science Division of the Dutch Research Council (NWO; project 08053), NWO grant 016.Vidi.189.050, and a Gravitation grant of the Netherlands Ministry of Education, Culture and Science and NWO (project 024.002.002 SIAM). B.K. was supported by the Villum foundation, Denmark (VYI Grant 25491).info:eu-repo/semantics/publishedVersio

The Periodic Spectroscopic Variability of FU Orionis

FU Orionis systems are young stars undergoing outbursts of disc accretion and where the optical spectrum contains lines associated with both the disc photosphere and a wind component. Previous observations of the prototype FU Orionis have suggested that the wind lines and the photospheric lines are modulated with periods of 14.54 and 3.54 days respectively (Herbig et al. 2003). We have re-observed the system at higher spectral resolution, by monitoring variations of optical line profiles over 21 nights in 2007 and have found periods of 13.48 and 3.6 days in the wind and disc components consistent with the above: this implies variability mechanisms that are stable over at least a decade. In addition we have found: i) that the variations in the photospheric absorption lines are confined to the blue wing of the line (around -9km/s): we tentatively ascribe this to an orbiting hotspot in the disc which is obscured by a disc warp during its receding phase. ii) The wind period is manifested not only in blue-shifted Halpha absorption, but also in red-shifted emission of Halpha and Hbeta, as well as in blue-shifted absorption of Na I D, Li I and Fe II. iii) We find that the periodic modulation of blue-shifted Halpha absorption at around -100km/s, is phase lagged with respect to variations in the other lines by ~1.8days. This is consistent with a picture in which variations at the wind base first affect chromospheric emission and then low velocity blue-shifted absorption, followed - after a lag equal to the propagation time of disturbances across the wind's acceleration region - by a response in high velocity blue-shifted absorption. Such arguments constrain the size of the acceleration region to ~10^12cm. We discuss possible mechanisms for periodic variations within the innermost 0.1AU of the disc, including the possibility that these variations indicate the presence of an embedded hot Jupiter.Comment: 20 pages, 23 figures. Accepted for publication in MNRAS. See http://www.ast.cam.ac.uk/~slp65/FUOripaperHRes.pdf for a pdf version of the paper with high-resolution images; footnote added to the titl

Shortfalls and Solutions for Meeting National and Global Conservation Area Targets

Governments have committed to conserving greater than or equal to 17% of terrestrial and greater than or equal to 10% of marine environments globally, especially areas of particular importance for biodiversity through ecologically representative Protected Area (PA) systems or other area-based conservation measures , while individual countries have committed to conserve 3-50% of their land area. We estimate that PAs currently cover 14.6% of terrestrial and 2.8% of marine extent, but 59-68% of ecoregions, 77-78% of important sites for biodiversity, and 57% of 25,380 species have inadequate coverage. The existing 19.7 million km super(2) terrestrial PA network needs only 3.3 million km super(2) to be added to achieve 17% terrestrial coverage. However, it would require nearly doubling to achieve, cost-efficiently, coverage targets for all countries, ecoregions, important sites, and species. Poorer countries have the largest relative shortfalls. Such extensive and rapid expansion of formal PAs is unlikely to be achievable. Greater focus is therefore needed on alternative approaches, including community- and privately managed sites and other effective area-based conservation measures

Proactive recruitment of cancer patients' social networks into a smoking cessation trial

This report describes the characteristics associated with successful enrollment of smokers in the social networks (i.e., family and close friends) of patients with lung cancer into a smoking cessation intervention

Protecting Important Sites for Biodiversity Contributes to Meeting Global Conservation Targets

Protected areas (PAs) are a cornerstone of conservation efforts and now cover nearly 13% of the world's land surface, with the world's governments committed to expand this to 17%. However, as biodiversity continues to decline, the effectiveness of PAs in reducing the extinction risk of species remains largely untested. We analyzed PA coverage and trends in species' extinction risk at globally significant sites for conserving birds (10,993 Important Bird Areas, IBAs) and highly threatened vertebrates and conifers (588 Alliance for Zero Extinction sites, AZEs) (referred to collectively hereafter as ‘important sites’). Species occurring in important sites with greater PA coverage experienced smaller increases in extinction risk over recent decades: the increase was half as large for bird species with>50% of the IBAs at which they occur completely covered by PAs, and a third lower for birds, mammals and amphibians restricted to protected AZEs (compared with unprotected or partially protected sites). Globally, half of the important sites for biodiversity conservation remain unprotected (49% of IBAs, 51% of AZEs). While PA coverage of important sites has increased over time, the proportion of PA area covering important sites, as opposed to less important land, has declined (by 0.45–1.14% annually since 1950 for IBAs and 0.79–1.49% annually for AZEs). Thus, while appropriately located PAs may slow the rate at which species are driven towards extinction, recent PA network expansion has under-represented important sites. We conclude that better targeted expansion of PA networks would help to improve biodiversity trends

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article