Inactivation of polyketide synthase and related genes results in the loss of complex lipids in Mycobacterium tuberculosis H37Rv

Aims: Phthiocerol dimycocerosate (PDIM) waxes and other lipids are necessary for successful Mycobacterium tuberculosis infection, although the exact role of PDIM in host-pathogen interactions remains unclear. In this study, we investigated the contribution of tesA, drrB, pks6 and pks11 genes in complex lipid biosynthesis in M. tuberculosis. Methods and Results: Four mutants were selected from M. tuberculosis H37Rv transposon mutant library. The transposon insertion sites were confirmed to be within the M. tuberculosis open reading frames for tesA (a probable thioesterase), drrB (predicted ABC transporter), pks11 (putative chalcone synthase) and pks6 (polyketide synthase). The first three of these transposon mutants were unable to generate PDIM and the fourth lacked novel polar lipids. Conclusions: Mycobacterium tuberculosis can be cultivated in vitro without the involvement of certain lipid synthesis genes, which may be necessary for in vivo pathogenicity. Significance and Impact of the Study: The use of transposon mutants is a new functional genomic approach for the eventual definition of the mycobacterial ‘lipidome’

Exploring the evolution and function of Canoe’s intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis

One central question for cell and developmental biologists is defining how epithelial cells can change shape and move during embryonic development without tearing tissues apart. This requires robust yet dynamic connections of cells to one another, via the cell-cell adherens junction, and of junctions to the actin and myosin cytoskeleton, which generates force. The last decade revealed that these connections involve a multivalent network of proteins, rather than a simple linear pathway. We focus on Drosophila Canoe, homolog of mammalian Afadin, as a model for defining the underlying mechanisms. Canoe and Afadin are complex, multidomain proteins that share multiple domains with defined and undefined binding partners. Both also share a long carboxy-terminal intrinsically disordered region (IDR), whose function is less well defined. IDRs are found in many proteins assembled into large multiprotein complexes. We have combined bioinformatic analysis and the use of a series of canoe mutants with early stop codons to explore the evolution and function of the IDR. Our bioinformatic analysis reveals that the IDRs of Canoe and Afadin differ dramatically in sequence and sequence properties. When we looked over shorter evolutionary time scales, we identified multiple conserved motifs. Some of these are predicted by AlphaFold to be alpha-helical, and two correspond to known protein interaction sites for alpha-catenin and F-actin. We next identified the lesions in a series of eighteen canoe mutants, which have early stop codons across the entire protein coding sequence. Analysis of their phenotypes are consistent with the idea that the IDR, including the conserved motifs in the IDR, are critical for protein function. These data provide the foundation for further analysis of IDR function. © 2023 Gurley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Preliminary assessment of the environmental baseline in the Fylde, Lancashire

This report presents the collated preliminary results from the British Geological Survey (BGS) led project Science-based environmental baseline monitoring associated with shale gas development in the Fylde, Lancashire. The project has been funded by a combination of BGS National Capability funding, in-kind contributions from project partners and a grant awarded by the Department of Business Energy and Investment Strategy (BEIS). It complements an on-going project, in which similar activities are being carried out, in the Vale of Pickering, North Yorkshire. Further information on the projects can be found on the BGS website: www.bgs.ac.uk. The project has initiated a wide-ranging environmental baseline monitoring programme that includes water quality (groundwater and surface water), seismicity, ground motion, atmospheric composition (greenhouse gases and air quality), soil gas and radon in air (indoors and outdoors). The motivation behind the project(s) was to establish independent monitoring in the area around the proposed shale gas hydraulic fracturing sites in the Fylde, Lancashire (Cuadrilla Resources Ltd) before any shale gas operations take place. As part of the project, instrumentation has been deployed to measure, in real-time or near real-time, a range of environmental variables (water quality, seismicity, atmospheric composition). These data are being displayed on the project’s web site (www.bgs.ac.uk/lancashire). Additional survey, sampling and monitoring has also been carried out through a co-ordinated programme of fieldwork and laboratory analysis, which has included installation of new monitoring infrastructure, to allow compilation of one of the most comprehensive environmental datasets in the UK. The monitoring programme is continuing. However, there are already some very important findings emerging from the limited datasets which should be taken into account when developing future monitoring strategy, policy and regulation. The information is not only relevant to Lancashire but will be applicable more widely in the UK and internationally. Although shale gas operations in other parts of the world are well-established, there is a paucity of good baseline data and effective guidance on monitoring. The project will also allow the experience gained, and the scientifically-robust findings to be used, to develop and establish effective environmental monitoring strategies for shale gas and similar industrial activities

Cassiopeia A, Cygnus A, Taurus A, and Virgo A at ultra-low radio frequencies

Context. The four persistent radio sources in the northern sky with the highest flux density at metre wavelengths are Cassiopeia A, Cygnus A, Taurus A, and Virgo A; collectively they are called the A-team. Their flux densities at ultra-low frequencies (< 100 MHz) can reach several thousands of janskys, and they often contaminate observations of the low-frequency sky by interfering with image processing. Furthermore, these sources are foreground objects for all-sky observations hampering the study of faint signals, such as the cosmological 21 cm line from the epoch of reionisation. Aims. We aim to produce robust models for the surface brightness emission as a function of frequency for the A-team sources at ultra-low frequencies. These models are needed for the calibration and imaging of wide-area surveys of the sky with low-frequency interferometers. This requires obtaining images at an angular resolution better than 15\u2033 with a high dynamic range and good image fidelity. Methods. We observed the A-team with the Low Frequency Array (LOFAR) at frequencies between 30 MHz and 77 MHz using the Low Band Antenna system. We reduced the datasets and obtained an image for each A-team source. Results. The paper presents the best models to date for the sources Cassiopeia A, Cygnus A, Taurus A, and Virgo A between 30 MHz and 77 MHz. We were able to obtain the aimed resolution and dynamic range in all cases. Owing to its compactness and complexity, observations with the long baselines of the International LOFAR Telescope will be required to improve the source model for Cygnus A further

Representational predicaments for employees: Their impact on perceptions of supervisors\u27 individualized consideration and on employee job satisfaction

A representational predicament for a subordinate vis-à-vis his or her immediate superior involves perceptual incongruence with the superior about the subordinate\u27s work or work context, with unfavourable implications for the employee. An instrument to measure the incidence of two types of representational predicament, being neglected and negative slanting, was developed and then validated through an initial survey of 327 employees. A subsequent substantive survey with a fresh sample of 330 employees largely supported a conceptual model linking being neglected and negative slanting to perceptions of low individualized consideration by superiors and to low overall job satisfaction. The respondents in both surveys were all Hong Kong Chinese. Two case examples drawn from qualitative interviews illustrate and support the conceptual model. Based on the research findings, we recommend some practical exercises to use in training interventions with leaders and subordinates. © 2013 Copyright Taylor and Francis Group, LLC

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

The Role of Radioactivities in Astrophysics

I present both a history of radioactivity in astrophysics and an introduction to the major applications of radioactive abundances to astronomy

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe