On the outside looking in: Redefining the role of analytical chemistry in the biosciences

© 2016 The Royal Society of Chemistry. Biomedical research has moved on from the study of the structure of organs, cells and organelles. Today, the key questions that must be addressed to understand the body in health and disease are related to fundamental biochemistry: the distribution and speciation of chemicals, the regulation of chemical reactions, and the control of chemical environments. To see advances in this field, it is essential for analytical chemists to actively engage in this process, from beginning to end. In this Feature Article, we review the progress that has been made towards gaining an understanding of the chemistry of the body, while commenting on the intrinsic disconnect between new innovations in the field of analytical chemistry and practical application within the biosciences. We identify the challenges that prevent chemists from making a greater impact in this field, and highlight key steps for moving forward

Metallobiology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent toxin used to selectively destroy dopaminergic neurons in the substantia nigra and induce parkinsonism. MPTP is metabolised to the 1-methyl-4-phenylpyridinium ion (MPP+) in glia, after which it enters the neuron via the dopamine transporter and results in elevated levels of oxidative stress. The mechanism through which MPP+ causes cell death is thought to involve redox-active metals, particularly iron (Fe). This review will examine how cellular metal metabolism is altered following MPTP insult, and how this relates to metal dyshomeostasis in idiopathic Parkinson's disease. This includes both cell damage arising from increased metal concentration, and how metal-binding proteins respond to MPTP-induced neurotoxicity. Implications for using MPTP as a model for human Parkinson's disease will be discussed in terms of cell metallobiology. © 2013 The Royal Society of Chemistry

Glutathione peroxidase 4: A new player in neurodegeneration?

© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity. We review recent studies of GPx4 with an emphasis on neuronal protection, and discuss the relevance of selenium levels on its enzymatic activity

A time-course analysis of changes in cerebral metal levels following a controlled cortical impact

© 2016 The Royal Society of Chemistry. Traumatic brain injury (TBI) is complicated by a sudden and dramatic change in brain metal levels, including iron (Fe), copper (Cu) and zinc (Zn). Specific 'metallo-pathological' features of TBI include increased non-heme bound Fe and the liberation of free Zn ions, both of which may contribute to the pathogenesis of TBI. To further characterise the metal dyshomeostasis that occurs following brain trauma, we performed a quantitative time-course survey of spatial Fe, Cu and Zn distribution in mice receiving a controlled cortical impact TBI. Images of brain metal levels produced using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) in the upper quadrant of the ipsilateral hemisphere were compared to the corresponding contralateral hemisphere, together with regional areas radiating toward the center of the brain from the site of lesion. Significant regional and time point specific elevations in Fe, Zn and Cu were detected immediately and up to 28 days after TBI. The magnitude and timeframe of many of these changes suggest that TBI results in a pronounced and sustained alteration in normal metal levels within the brain. Such alterations are likely to play a role in both the short- and long-term consequences of head trauma and suggest that pharmacological modulation to normalize these metal levels may be efficacious in improving functional outcome

Superoxide Dismutase 1 in Health and Disease: How a Frontline Antioxidant Becomes Neurotoxic.

Cu/Zn superoxide dismutase (SOD1) is a frontline antioxidant enzyme catalysing superoxide breakdown and is important for most forms of eukaryotic life. The evolution of aerobic respiration by mitochondria increased cellular production of superoxide, resulting in an increased reliance upon SOD1. Consistent with the importance of SOD1 for cellular health, many human diseases of the central nervous system involve perturbations in SOD1 biology. But far from providing a simple demonstration of how disease arises from SOD1 loss-of-function, attempts to elucidate pathways by which atypical SOD1 biology leads to neurodegeneration have revealed unexpectedly complex molecular characteristics delineating healthy, functional SOD1 protein from that which likely contributes to central nervous system disease. This review summarises current understanding of SOD1 biology from SOD1 genetics through to protein function and stability

Chimpanzees do not take into account what others can hear in a competitive situation

Chimpanzees (Pan troglodytes) know what others can and cannot see in a competitive situation. Does this reflect a general understanding the perceptions of others? In a study by Hare et al. (2000) pairs of chimpanzees competed over two pieces of food. Subordinate individuals preferred to approach food that was behind a barrier that the dominant could not see, suggesting that chimpanzees can take the visual perspective of others. We extended this paradigm to the auditory modality to investigate whether chimpanzees are sensitive to whether a competitor can hear food rewards being hidden. Results suggested that the chimpanzees did not take what the competitor had heard into account, despite being able to locate the hiding place themselves by the noise

Correction: Detecting antimicrobial resistance in Escherichia coli using benchtop attenuated total reflectance-Fourier transform infrared spectroscopy and machine learning.

Correction for 'Detecting antimicrobial resistance in Escherichia coli using benchtop attenuated total reflectance-Fourier transform infrared spectroscopy and machine learning' by Hewa G. S. Wijesinghe et al., Analyst, 2021, DOI: 10.1039/d1an00546d

Health outcomes of iron supplementation and/or food fortification in iron-replete children aged 4-24 months: Protocol for a systematic review and meta-analysis

© 2019 The Author(s). Background: Direct supplementation or food fortification with iron are two public health initiatives intended to reduce the prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA) in 4-24-month-old infants. In most high-income countries where IDA prevalence is 40%. Emerging concerns about delayed neurological effects of early-life iron overexposure have raised questions as to whether recommended guidelines in high-income countries are unnecessarily excessive. This systematic review will gather evidence from supplementation/fortification trials, comparing health outcomes in studies where iron-replete children did or did not receive additional dietary iron; and determine if replete children at study outset were not receiving additional iron show changes in haematological indices of ID/IDA over the trial duration. Methods: We will perform a systematic review of the literature, including all studies of iron supplementation and/or fortification, including study arms with confirmed iron-replete infants at the commencement of the trial. This includes both dietary iron intervention or placebo/average dietary intakes. One reviewer will conduct searches in electronic databases of published and ongoing trials (Medline, Web of Science, Scopus, CENTRAL, EBSCO [e.g. CINAHL Complete, Food Science and Technology Abstracts], Embase, ClinicalTrials.gov, ClinicalTrialsRegister.eu and who.it/trialsearch), digital theses and dissertations (WorldCat, Networked Digital Library of Theses and Dissertations, DART-Europe E-theses Portal, Australasian Digital Theses Program, Theses Canada Portal and ProQuest). For eligible studies, one reviewer will use a data extraction form, and a second reviewing entered data for accuracy. Both reviewers will independently perform quality assessments before qualitative and, if appropriate, quantitative synthesis as a meta-analysis. We will resolve any discrepancies through discussion or consult a third author to resolve discrepancies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement will be used as the basis for reporting. Discussion: Recommended iron supplementation and food fortification practices in high-income countries have been criticised for being both excessive and based on outdated or underpowered studies. This systematic review will build a case for revisiting iron intake guidelines for infants through the design of new trials where health effects of additional iron intake in iron-replete infants are the primary outcome. Systematic review registration: PROSPERO CRD42018093744

φxANES: In vivo imaging of metal-protein coordination environments

© 2016, Nature Publishing Group. All rights reserved. We have developed an X-ray absorption near edge structure spectroscopy method using fluorescence detection for visualizing in vivo coordination environments of metals in biological specimens. This approach, which we term fluorescence imaging XANES (φXANES), allows us to spatially depict metal-protein associations in a native, hydrated state whilst avoiding intrinsic chemical damage from radiation. This method was validated using iron-challenged Caenorhabditis elegans to observe marked alterations in redox environment