Iron accumulates in the primate choroid of the eye with aging as revealed with synchrotron X-ray fluorescence microscopy

Aging leads to an increase in iron-loaded cellular structures in the choroid of the eye. This study was carried out to determine the distribution and content of iron, zinc and copper in the macular retina, choroid and retrobulbar optic nerve of young (4–5 years, n = 3) and aged (15–16 years, n = 5) male non-human primates, Macaca fascicularis, whose ocular anatomy is similar to humans. Thirty μm-thick tissue sections were analysed with synchrotron X-ray fluorescence and stained histologically for iron deposition. Quantitative measurements showed high levels of iron, zinc and copper in the choroid and retinal pigment epithelium in the macular area and arachnoid layer in the retrobulbar optic nerve. In aged animals compared to young ones, there was an increase in iron in the choroid with larger deposits and iron-loaded cellular structures. Iron-accumulation within these cellular structures may contribute to choroidal function impairment in aging and age-related macular degeneration

RELICT FORSTERITE IN UNEQUILIBRATED ENSTATITE CHONDRITES

82nd Annual Meeting of The Meteoritical Society 2019 (LPI Contrib. No. 2157). This is freely available from the LPI website. No copyright statement available

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

Emerging patterns in the distribution of trace elements in ovarian, invasive and in-situ breast cancer

Breast cancer is the most common cancer and ovarian cancer is the 8th most common cancer affecting women worldwide. This study highlights the changes of trace element levels accompanied by the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) of the breast, using micro probe Synchrotron Radiation X-ray Fluorescence (μSRXRF). The average values for the increase in Ca, Fe and Zn in tumour regions with respect to surrounding regions for the DCIS samples were significantly higher compared to the increase in the IDC samples (P <0.01).This study was also carried out to find a connection between ovarian cancer and breast cancer with respect to the cellular distribution of Ca, Cu, Fe, and Zn. For IDC, DCIS and ovarian cases, the statistical analysis reveals a significant increase in the levels of Ca, Cu and Zn concentrations in cancer tissue when compared to the normal surrounding tissue. For Fe, the differences between tumour regions with respect to surrounding regions were found to be not significant in IDC and ovarian cases. In DCIS cases, the results reveal a significant increase in the levels of Fe in cancer tissue when compared to the surrounding normal breast tissue (P <0.01)

Aging results in iron accumulations in the non-human primate choroid of the eye without an associated increase in zinc, copper or sulphur

We present further analyses of a previous experiment published in 2016 where the distribution, concentration and correlation of iron, zinc, copper and sulphur in the choroid of the eye in young and aged old world primates (Macaca fascicularis) was studied with synchrotron X-ray fluorescence with a 2 μm resolution. The results indicate that iron accumulates in hotspots in the choroid with age with fluorescence intensity ranging from 2- to 7-fold (1002–3752 ppm) the mean level in the choroidal stroma (500 ppm) and maximum iron levels in blood vessel lumina. Iron hotspots with iron ppm > 1000 preferentially contained Fe3+ as demonstrated by Perls staining. There was a strong spatial co-localisation and correlation between copper and zinc (Pearson’s correlation coefficient 0.97), and both elements with sulphur in the choroid of young animals. However, these are reduced in the choroid of aged animals and lost in the iron hotspots. The lack of proportional co-distribution suggests that iron accumulation does not induce a concomitant increase in zinc, copper or zinc-, copper-metalloproteins. It is possible that the iron hotspots are ferritin or hemosiderin molecules loaded with Fe3+ in stable, insoluble, non-toxic complexes without a significant oxidative environment

Chemical imaging of single catalyst particles with scanning μ-XANES-CT and μ-XRF-CT

The physicochemical state of a catalyst is a key factor in determining both activity and selectivity; however these materials are often not structurally or compositionally homogeneous. Here we report on the 3-dimensional imaging of an industrial catalyst, Mo-promoted colloidal Pt supported on carbon. The distribution of both the active Pt species and Mo promoter have been mapped over a single particle of catalyst using microfocus X-ray fluorescence computed tomography. X-ray absorption near edge spectroscopy (XANES) and extended X-ray absorption fine structure revealed a mixed local coordination environment, including the presence of both metallic Pt clusters and Pt chloride species, but also no direct interaction between the catalyst and Mo promoter. We also report on the benefits of scanning μ-XANES computed tomography for chemical imaging, allowing for 2- and 3-dimensional mapping of the local electronic and geometric environment, in this instance for both the Pt catalyst and Mo promoter throughout the catalyst particle

Posterior Reversible Encephalopathy Syndrome Associated with Oxaliplatin Use for Pancreatic Adenocarcinoma

The posterior reversible encephalopathy syndrome (PRES) was first described by Hinchey’s group in 1996 as a reversible vasogenic brain edema on magnetic resonance imaging (MRI). Hypertension represents the most frequent manifestation associated with PRES. In the present report, we present a patient diagnosed with locally advanced pancreatic adenocarcinoma who received 3 cycles of a 5-fluoruracil plus oxaliplatin-based chemotherapy regimen and developed PRES after the third cycle. Several days after receiving the second cycle of FOLFOX chemotherapy, the patient started having episodes of hypertensive crisis (systolic pressure = 180, diastolic pressure = 100), that was controlled with amlodipine, irbesartan, and hydrochlorothiazide. After the administration of the third cycle, this time with the FOLFIRINOX regimen, he appeared lethargic and disoriented in place and time. MRI revealed bilateral areas of signal hyperintensity in the thalamus, hypothalamus, fibers of reticular formation, anterior section of cerebral vermis and a mild edema of left parahippocampal gyrus, with no signs of brain metastases. Ultimately, the patient was diagnosed with PRES syndrome, and he was treated with glucose, 5% saline, thiamine supplementation, levetiracetam (Keppra®), and i.v. dexamethasone. Three weeks later, he gradually became conscious, with cognitive function recovery, and capable of executing movements

Controlled fabrication of osmium nanocrystals by electron, laser and microwave irradiation and characterisation by microfocus X-ray absorption spectroscopy

YesOsmium nanocrystals can be fabricated by electron (3–50 nm, formed by atom migration), 785–815 nm laser (20–50 nm, in micelle islands), and microwave (ca. 1 nm in arrays, >100 mg scale) irradiation of a polymer-encapsulated OsII carborane; microfocus X-ray absorption studies at the Os LIII-edge show differences between the three preparation methods, suggesting that the electron-beam irradiated materials have a significant support interaction and/or surface oxidation, while the laser and microwave samples are more like metallic osmium.Royal Society (University Research Fellowship No. UF150295 to NPEB), the Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the ERC (Grant No. 247450 to PJS), EPSRC (Grant No. EP/F034210/1 to PJS and EP/ J007153/1 to VGS), Diamond Light Source (Beam-time grant number SP11314)

Nanoparticles as multimodal photon transducers of ionizing radiation

In biomedical imaging, nanoparticles combined with radionuclides that generate Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies, and as activatable probes. In these applications, the nanoparticle is often viewed as a carrier inert to ionizing radiation from the radionuclide. However, certain phenomena such as enhanced nanoparticle luminescence and generation of reactive oxygen species cannot be explained by only Cerenkov luminescence interactions with nanoparticles. Herein, we report methods to examine the mechanisms of nanoparticle excitation by radionuclides, including interactions with Cerenkov luminescence, β particles, and γ radiation. We demonstrate that β scintillation contributes appreciably to excitation and reactivity in certain nanoparticle systems and that excitation of nanoparticles composed of large atomic number atoms by radionuclides generates X-rays, enabling multiplexed imaging through single photon emission computed tomography. These findings demonstrate practical optical imaging and therapy using radionuclides with emission energies below the Cerenkov threshold, thereby expanding the list of applicable radionuclides

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