The Power of Light Zine 2 - Why does life exist? - an epistemically insightful way to explore the nature of science and research at Diamond Light Source, UK

In the STFC funded Epistemic Insight Initiative project, The Power of Light, a series of resources have been designed informed by co-creation activities, pilot lessons, and workshops that involved children in schools and with their families in community spaces. Through this project with Diamond, we brought into classrooms and community spaces how light can be used to help investigate the world around us, address real-world problems and inform our thinking about Big Questions. The resources we develop support teachers' and their students' sense of agency when exploring 'how knowledge works' and how knowledge is built through different disciplines (including the natural sciences, the arts, and the humanities). This 'zine', with its focus on how scientists have been working with paleotonologists to investigate evidence, found inside the fossilised leg of a thescelosaurus, of the cataclysmic event that led to the extinction of dinosaurs. Zine 2 'Why does life exist?' has been developed through co-creative activities involving research scientists at Diamond Light Source (UK), academics, primary school teachers, STEM ambassadors, and Diamond's public engagement team. Zines use an appealing combination of text and images to create a concise comic-like narrative format to generate enthusiasm about a particular area of interest - the series of zines designed for this project focuses on research taking place at the Diamond facility. The Diamond Light Source facility houses a synchrotron which is used to conduct research in a variety of applied fields of science and technology. This zine is designed to be accessible to ages 8+, and works well with a short animation (available in both Zenodo and on the Epistemic Insight You Tube channel) that has been created with additional funding from STFC. Teaching notes are available for this zine, with guidance and activity sheets to support working with the Power of Light resources. This zine explores these discussion questions: 1) What is needed for living things to exist on Earth? 2) What helps us to learn more about past events? 3) What enables us to be able say we 'know' something

Implications of X-ray beam profiles on qualitative and quantitative synchrotron micro-focus X-ray fluorescence microscopy

Synchrotron radiation X-ray fluorescence microscopy is frequently used to investigate the spatial distribution of elements within a wide range of samples. Interrogation of heterogeneous samples that contain large concentration ranges has the potential to produce image artefacts due to the profile of the X-ray beam. The presence of these artefacts and the distribution of flux within the beam profile can significantly affect qualitative and quantitative analyses. Two distinct correction methods have been generated by referencing the beam profile itself or by employing an adaptive-thresholding procedure. Both methods significantly improve qualitative imaging by removing the artefacts without compromising the low-intensity features. The beam-profile correction method improves quantitative results but requires accurate two-dimensional characterization of the X-ray beam profile

Synchrotron analysis of human organ tissue exposed to implant material

Background Orthopaedic implants made of cobalt-chromium alloy undergo wear and corrosion that can lead to deposition of cobalt and chromium in vital organs. Elevated cardiac tissue cobalt levels are associated with myocardial injury while chromium is a well-established genotoxin. Though metal composition of tissues surrounding hip implants has been established, few investigators attempted to characterize the metal deposits in systemic tissues of total joint arthroplasty patients. Methods We report the first use of micro-X-ray fluorescence coupled with micro-X-ray absorption spectroscopy to probe distribution and chemical form of cobalt, chromium and titanium in postmortem samples of splenic, hepatic and cardiac tissue of patients with metal-on-polyethylene hip implants (n = 5). Results Majority of the cobalt was in the 2+ oxidation state, while titanium was present exclusively as titanium dioxide, in either rutile or anatase crystal structure. Chromium was found in a range of forms including a highly oxidised, carcinogenic species (CrV/VI), which has never been identified in human tissue before. Conclusions Carcinogenic forms of chromium might arise in vital organs of total joint arthroplasty patients. Further studies are warranted with patients with metal-on-metal implants, which tend to have an increased release of cobalt and chromium compared to metal-on-polyethylene hips

Metallome of cerebrovascular endothelial cells infected with Toxoplasma gondii using μ-XRF imaging and inductively coupled plasma mass spectrometry

In this study, we measured the levels of elements in human brain microvascular endothelial cells (ECs) infected with T. gondii. ECs were infected with tachyzoites of the RH strain, and at 6, 24, and 48 hours post infection (hpi), the intracellular concentrations of elements were determined using a synchrotron–microfocus X-ray fluorescence microscopy (μ-XRF) system. This method enabled the quantification of the concentrations of Zn and Ca in infected and uninfected (control) ECs at sub-micron spatial resolution. T. gondii-hosting ECs contained less Zn than uninfected cells only at 48 hpi (p 0.05). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis revealed infection-specific metallome profiles characterized by significant increases in the intracellular levels of Zn, Fe, Mn and Cu at 48 hpi (p < 0.01), and significant reductions in the extracellular concentrations of Co, Cu, Mo, V, and Ag at 24 hpi (p < 0.05) compared with control cells. Zn constituted the largest part (74%) of the total metal composition (metallome) of the parasite. Gene expression analysis showed infection-specific upregulation in the expression of five genes, MT1JP, MT1M, MT1E, MT1F, and MT1X, belonging to the metallothionein gene family. These results point to a possible correlation between T. gondii infection and increased expression of MT1 isoforms and altered intracellular levels of elements, especially Zn and Fe. Taken together, a combined μ-XRF and ICP-MS approach is promising for studies of the role of elements in mediating host–parasite interaction

Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells

INTRODUCTION: A physiological feature of many tumor tissues and cells is the tendency to accumulate high concentrations of copper. While the precise role of copper in tumors is cryptic, copper, but not other trace metals, is required for angiogenesis. We have recently reported that organic copper-containing compounds, including 8-hydroxyquinoline-copper(II) and 5,7-dichloro-8-hydroxyquinoline-copper(II), comprise a novel class of proteasome inhibitors and tumor cell apoptosis inducers. In the current study, we investigate whether clioquinol (CQ), an analog of 8-hydroxyquinoline and an Alzheimer's disease drug, and pyrrolidine dithiocarbamate (PDTC), a known copper-binding compound and antioxidant, can interact with copper to form cancer-specific proteasome inhibitors and apoptosis inducers in human breast cancer cells. Tetrathiomolybdate (TM), a strong copper chelator currently being tested in clinical trials, is used as a comparison. METHODS: Breast cell lines, normal, immortalized MCF-10A, premalignant MCF10AT1K.cl2, and malignant MCF10DCIS.com and MDA-MB-231, were treated with CQ or PDTC with or without prior interaction with copper, followed by measurement of proteasome inhibition and cell death. Inhibition of the proteasome was determined by levels of the proteasomal chymotrypsin-like activity and ubiquitinated proteins in protein extracts of the treated cells. Apoptotic cell death was measured by morphological changes, Hoechst staining, and poly(ADP-ribose) polymerase cleavage. RESULTS: When in complex with copper, both CQ and PDTC, but not TM, can inhibit the proteasome chymotrypsin-like activity, block proliferation, and induce apoptotic cell death preferentially in breast cancer cells, less in premalignant breast cells, but are non-toxic to normal/non-transformed breast cells at the concentrations tested. In contrast, CQ, PDTC, TM or copper alone had no effects on any of the cells. Breast premalignant or cancer cells that contain copper at concentrations similar to those found in patients, when treated with just CQ or PDTC alone, but not TM, undergo proteasome inhibition and apoptosis. CONCLUSION: The feature of breast cancer cells and tissues to accumulate copper can be used as a targeting method for anticancer therapy through treatment with novel compounds such as CQ and PDTC that become active proteasome inhibitors and breast cancer cell killers in the presence of copper

Assessing the atmospheric S burden of continental flood basalts through synchrotron light micro-XRF

Severe forcing of Large Igneous Provinces (LIPs) on the environment through massive outpours of volcanic gases such as SO2 and CO2 (Self et al., 2008) is suggested by their synchrony with major Phanerozoic mass extinctions, but gas contents of the basalts and gas emission rates are poorly constrained. Here we deal with three LIPs that are synchronous with, and may have triggered, major biotic crises, namely Siberian Traps (end-Permian, c. 250 Ma), CAMP (Central Atlantic magmatic province; end-Triassic, c. 201 Ma) and Deccan Traps (end-Cretaceous, c. 66 Ma) and two LIPs whose emplacement only had a minor impact on the biosphere, i.e. Early Jurassic Karoo-Ferrar (c. 181 Ma) and Early Cretaceous Paran\ue0-Etendeka (PE, c. 134 Ma). Classically, the gas load of a continental flood basalt (CFB) is estimated through analyses of melt-inclusions from early crystallized olivines in degassed flows (Self et al., 2008), but these investigations may be hindered by the paucity of fresh olivine phenocrysts, as for CAMP or PE. Hence, here we illustrate an alternative approach in which the pyroxene/melt sulfur partition coefficient (KD) was appraised on experimentally crystallized clinopyroxenes (augites) from sulphide-saturated basalts (at 525 MPa and 1200\ub0 or 1175\ub0C in a piston-cylinder apparatus). S (and Cl) contents were then measured by in-situ micro-XRF (Diamond synchrotron, UK) in augite phenocrysts from rocks chemically representative of the above mentioned LIPs. The magmatic S burden was thus calculated through the experimentally determined KD, starting from the analyzed S in clinopyroxenes. Transmission electron microscopy (TEM) analyses discarded any presence of sulphide or fluid inclusions in (CAMP) clinopyroxenes, thus justifying the use of the KD approach, which hinges on the concept of S being distributed at equilibrium between the magma and the crystal lattice. Data are presently available only for CAMP, PE and Deccan, but will shortly be completed with those from the remaining provinces. So far, S contents for Deccan basalts (0.04- 0.14 wt.%) are consistent with those obtained by Self et al. (2008) on melt inclusions. No paramount differences are highlighted between CFB provinces, but, surprisingly, PE high-Ti and CAMP low-Ti samples show the highest and lowest S values, respectively. Rationales for the decoupling between volcanic gas burden and severity of biotic crisis may either be due to PE magmas being emplaced during weaker magmatic pulses at lower eruption rates or S not being the primary cause of environmental perturbations (in favor of CO2 or other gases). Another hypothesis though hinges on the oxidation state of magmas influencing S solubility (Moretti and Baker, 2008). In this sense, strongly oxidized PE high-Ti basaltic magmas would have retained more S, with consequent reduced gas emissions and minor environmental impact