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"Brown, Alan"
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WHO Environmental Noise Guidelines for the European Region: A Systematic Review of Transport Noise Interventions and Their Impacts on Health
This paper describes a systematic review (1980–2014) of evidence on effects of transport noise interventions on human health. The sources are road traffic, railways, and air traffic. Health outcomes include sleep disturbance, annoyance, cognitive impairment of children and cardiovascular diseases. A conceptual framework to classify noise interventions and health effects was developed. Evidence was thinly spread across source types, outcomes, and intervention types. Further, diverse intervention study designs, methods of analyses, exposure levels, and changes in exposure do not allow a meta-analysis of the association between changes in noise level and health outcomes, and risk of bias in most studies was high. However, 43 individual transport noise intervention studies were examined (33 road traffic; 7 air traffic; 3 rail) as to whether the intervention was associated with a change in health outcome. Results showed that many of the interventions were associated with changes in health outcomes irrespective of the source type, the outcome or intervention type (source, path or infrastructure). For road traffic sources and the annoyance outcome, the expected effect-size can be estimated from an appropriate exposure–response function, though the change in annoyance in most studies was larger than could be expected based on noise level change.
Journal Article
Structure of a microtubule-bound axonemal dynein
Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating, a process critical for cellular motility and extracellular fluid flow. Axonemal dyneins are evolutionarily and biochemically distinct from cytoplasmic dyneins that transport cargo, and the mechanisms regulating their localization and function are poorly understood. Here, we report a single-particle cryo-EM reconstruction of a three-headed axonemal dynein natively bound to doublet microtubules isolated from cilia. The slanted conformation of the axonemal dynein causes interaction of its motor domains with the neighboring dynein complex. Our structure shows how a heterotrimeric docking complex specifically localizes the linear array of axonemal dyneins to the doublet microtubule by directly interacting with the heavy chains. Our structural analysis establishes the arrangement of conserved heavy, intermediate and light chain subunits, and provides a framework to understand the roles of individual subunits and the interactions between dyneins during ciliary waveform generation.
Axonemal dyneins are tethered to doublet microtubules inside cilia to drive ciliary beating but the mechanisms regulating their localization and function are poorly understood. Here authors report a cryo-EM reconstruction of a three-headed axonemal dynein natively bound to doublet microtubules isolated from cilia which provides a framework to understand the roles of individual subunits.
Journal Article
The structure of the yeast mitochondrial ribosome
Mitochondria have specialized ribosomes (mitoribosomes) dedicated to the expression of the genetic information encoded by their genomes. Here, using electron cryomicroscopy, we have determined the structure of the 75-component yeast mitoribosome to an overall resolution of 3.3 angstroms. The mitoribosomal small subunit has been built de novo and includes 15S ribosomal RNA (rRNA) and 34 proteins, including 14 without homologs in the evolutionarily related bacterial ribosome. Yeast-specific rRNA and protein elements, including the acquisition of a putatively active enzyme, give the mitoribosome a distinct architecture compared to the mammalian mitoribosome. At an expanded messenger RNA channel exit, there is a binding platform for translational activators that regulate translation in yeast but not mammalian mitochondria. The structure provides insights into the evolution and species-specific specialization of mitochondrial translation.
Journal Article
Rumpelstiltskin : an interactive fairy tale adventure
In this You Choose adventure, the miller's daughter has to turn seaweed into oxygen in a bubble city on a polluted Earth, a middle school student has to complete binders of math problems, and a lonely magical hermit's offers of assistance stem from his desire for friendship--the reader chooses which plot to pursue.
Book
Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model
The 2017 American College of Neuropychopharmacology (ACNP) conference hosted a Study Group on 4 December 2017, Establishing best practice guidelines to improve the rigor, reproducibility, and transparency of the maternal immune activation (MIA) animal model of neurodevelopmental abnormalities. The goals of this session were to (a) evaluate the current literature and establish a consensus on best practices to be implemented in MIA studies, (b) identify remaining research gaps warranting additional data collection and lend to the development of evidence-based best practice design, and (c) inform the MIA research community of these findings. During this session, there was a detailed discussion on the importance of validating immunogen doses and standardizing the general design (e.g., species, immunogenic compound used, housing) of our MIA models both within and across laboratories. The consensus of the study group was that data does not currently exist to support specific evidence-based model selection or methodological recommendations due to lack of consistency in reporting, and that this issue extends to other inflammatory models of neurodevelopmental abnormalities. This launched a call to establish a reporting checklist focusing on validation, implementation, and transparency modeled on the ARRIVE Guidelines and CONSORT (scientific reporting guidelines for animal and clinical research, respectively). Here we provide a summary of the discussions in addition to a suggested checklist of reporting guidelines needed to improve the rigor and reproducibility of this valuable translational model, which can be adapted and applied to other animal models as well.
Journal Article