B16-Test Beamline
I16-Materials and Magnetism
I18-Microfocus Spectroscopy
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Diamond Proposal Number(s):
[15884, 15926, 11645]
Open Access
Abstract: Our bone health as an adult is defined by patterns of development in early life, with perturbed growth during fetal and neonatal periods predisposing individuals to poor bone health in adulthood. Studies have identified poor maternal diet during pregnancy as a critical factor in shaping offspring bone development, with significant impacts on adult bone structure and health. However, the association between a father’s diet and the bone health of his offspring remains poorly defined. To address this knowledge gap, we fed male C57BL/6 mice either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 8 weeks. Using these males, we generated offspring through artificial insemination, in combination with vasectomised male mating. Using this approach, we derived offspring from either NPD or LPD sperm but in the presence of NPD or LPD seminal plasma. Using micro-computed tomography and synchrotron X-ray diffraction, we observed significant changes in offspring femur morphology and hydroxyapatite crystallographic parameters from just 3 weeks of age in offspring derived from LPD sperm or seminal plasma. We also observed that differential femur morphology and hydroxyapatite crystallographic parameters were maintained into adulthood and into a second generation. Analysis of paternal sperm identified a down regulation of 26 osteogenic genes associated with extracellular matrix levels and maintenance, transcription and growth factors and bone ossification. These observations indicate that poor paternal diet at the time of conception affects offspring bone development and morphology in an age and generation specific manner.
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Oct 2025
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I18-Microfocus Spectroscopy
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Diamond Proposal Number(s):
[35162]
Open Access
Abstract: Enamel erosion alters the structural integrity of the tooth surface, which can be measured using indentation techniques. However, traditional single-load indentation methods assume homogeneity within the eroded enamel, overlooking potential stratification within the subsurface lesion. This study investigates the presence of mechanical and porosity gradients within the enamel following simulated dietary acid exposure and examines how lesion depth and structure change with continued erosion. We applied varying-load micro-indentation to human enamel subjected to citric acid challenge, revealing a distinct stratification of mechanical properties. A soft superficial layer (~1- to 2-µm thick) exhibited significantly reduced hardness and was easily removed by ultrasonication, indicating its fragility. Beneath this layer, mechanical properties stabilized despite prolonged acid exposure (~3 min), suggesting a saturation point in lesion development. Profilometric analysis confirmed that although material loss increased with erosion time, the depth of the altered subsurface zone remained constant. To explore the porosity distribution, we used a novel gold nanoparticle labeling technique coupled with synchrotron-based X-ray fluorescence imaging. Nanoparticles (~20 nm) penetrated to depths of 15 to 20 µm, aligning closely with mechanical gradients inferred from indentation measurements. These findings indicate that subsurface enamel exhibits not only mechanical stratification but also corresponding variations in porosity. Our results demonstrate the limitations of single-load indentation in characterizing erosion-affected enamel and highlight the utility of multiload approaches in detecting structural heterogeneity. The correlation between mechanical softening and increased porosity suggests that the enamel subsurfaces are differentially affected. These findings raise important implications for therapeutic intervention: should remineralization strategies shift from bulk mineral delivery to layer-specific, functionally informed repair?
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Oct 2025
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I18-Microfocus Spectroscopy
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Diamond Proposal Number(s):
[35162]
Open Access
Abstract: The quantitative characterization of the structure of biomineral surfaces is needed for guiding regenerative strategies. Current techniques are compromised by a requirement for extensive sample preparation, limited length-scales, or the inability to repeatedly measure the same surface over time and monitor structural changes. We aim to address these deficiencies by developing Calcium (Ca) K-edge Polarisation Induced Contrast X-ray Fluorescence (PIC-XRF) to quantify hydroxyapatite (HAp) crystallite structural arrangements in high and low textured surfaces. Minimally prepared human dental enamel was used as an exemplar to quantify initial surface structures, and the disruption caused by short dietary acid exposures. By measuring surfaces at different rotational angles relative to a polarised focused (2x2µm) monochromatic X-ray source (at either 4049.2 and 4051.1 eV) it was possible to discriminate the principal and secondary orientations of surface crystallites, along with their texture. It was also possible to quantify the organisation of crystallites in both low (enamel cross-sections) and highly textured (facial enamel) surfaces including the identification of crystallites aligned perpendicular to the surface—a challenge for other synchrotron techniques. Surface modifications following short term acid erosion (affecting <20µm of the enamel surface depth) were detected as significant shifts in principal crystallite orientation (p<0.001) and as a marked reduction in surface texture (p<0.001). Findings suggest preferential dissolution of HAp based on crystallite angular orientation. We demonstrate that PIC-XRF is a powerful tool to quantify biomineral surfaces, with minimal sample preparation that enables monitoring of surface structural changes through repeated measurements.
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Jan 2025
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B16-Test Beamline
I18-Microfocus Spectroscopy
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Aaron R. H.
Leblanc
,
Alexander P.
Morrell
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Slobodan
Sirovica
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Maisoon
Al-Jawad
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David
Labonte
,
Domenic C.
D’amore
,
Christofer
Clemente
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Siyang
Wang
,
Finn
Giuliani
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Catriona M.
Mcgilvery
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Michael
Pittman
,
Thomas G.
Kaye
,
Colin
Stevenson
,
Joe
Capon
,
Benjamin
Tapley
,
Simon
Spiro
,
Owen
Addison
Diamond Proposal Number(s):
[22284, 26050]
Open Access
Abstract: Komodo dragons (Varanus komodoensis) are the largest extant predatory lizards and their ziphodont (serrated, curved and blade-shaped) teeth make them valuable analogues for studying tooth structure, function and comparing with extinct ziphodont taxa, such as theropod dinosaurs. Like other ziphodont reptiles, V. komodoensis teeth possess only a thin coating of enamel that is nevertheless able to cope with the demands of their puncture–pull feeding. Using advanced chemical and structural imaging, we reveal that V. komodoensis teeth possess a unique adaptation for maintaining their cutting edges: orange, iron-enriched coatings on their tooth serrations and tips. Comparisons with other extant varanids and crocodylians revealed that iron sequestration is probably widespread in reptile enamels but it is most striking in V. komodoensis and closely related ziphodont species, suggesting a crucial role in supporting serrated teeth. Unfortunately, fossilization confounds our ability to consistently detect similar iron coatings in fossil teeth, including those of ziphodont dinosaurs. However, unlike V. komodoensis, some theropods possessed specialized enamel along their tooth serrations, resembling the wavy enamel found in herbivorous hadrosaurid dinosaurs. These discoveries illustrate unexpected and disparate specializations for maintaining ziphodont teeth in predatory reptiles.
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Jul 2024
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I18-Microfocus Spectroscopy
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Alexander P.
Morrell
,
Richard A.
Martin
,
Helen M
Roberts
,
Hiram
Castillo-Michel
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J. Frederick W.
Mosselmans
,
Kalotina
Geraki
,
Adrian T.
Warfield
,
Paul
Lingor
,
Wasif
Qayyum
,
Daniel
Graf
,
Maria
Febbraio
,
Owen
Addison
Diamond Proposal Number(s):
[17638, 23569]
Open Access
Abstract: Exposures to exogenous particles is of increasing concern to human health. Characterising the concentrations, chemical species, distribution, and involvement of the stimulus with the tissue microanatomy is essential in understanding the associated biological response. However, no single imaging technique can interrogate all these features at once which confounds and limits correlative analyses. Developments of synchronous imaging strategies, allowing multiple features to be identified simultaneously, is essential to assess spatial relationships between these key features with greater confidence. Here we present data to first highlight complications of correlative analysis between the tissue microanatomy and elemental composition associated with imaging serial tissue sections. This is achieved by assessing both the cellular and elemental distribution in 3-dimensional space using optical microscopy on serial sections and confocal X-ray fluorescence spectroscopy on bulk samples respectively. We propose a new imaging strategy using lanthanide tagged antibodies with X-ray fluorescence spectroscopy. Using simulations, a series of lanthanide tags were identified as candidate labels for scenarios where tissue sections are imaged. The feasibility and value of the proposed approach is shown where an exposure of Ti was identified concurrently with CD45 positive cells at sub-cellular resolutions. Significant heterogeneity in the distribution of exogenous particles and cells can be present between immediately adjacent serial sections showing clear need of synchronous imaging methods. The proposed approach enables elemental compositions to be correlated with the tissue microanatomy in a highly multiplexed and non-destructive manner at high spatial resolutions with the opportunity for subsequent guided analysis.
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May 2023
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I18-Microfocus Spectroscopy
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Garrit
Koller
,
Alexander P.
Morrell
,
Rui Pedro
Galão
,
Suzanne
Pickering
,
Eithne
Macmahon
,
Joanna
Johnson
,
Konstantin
Ignatyev
,
Stuart J. D.
Neil
,
Sherif
Elsharkawy
,
Roland
Fleck
,
Pedro Miguel Pereira
Machado
,
Owen
Addison
Diamond Proposal Number(s):
[28216]
Abstract: Containing the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented challenge due to high horizontal transmissivity and asymptomatic carriage rates. Lateral flow device (LFD) immunoassays were introduced in late 2020 to detect SARS-CoV-2 infection in asymptomatic or presymptomatic individuals rapidly. While LFD technologies have been used for over 60 years, their widespread use as a public health tool during a pandemic is unprecedented. By the end of 2020, data from studies into the efficacy of the LFDs emerged and showed these point-of-care devices to have very high specificity (ability to identify true negatives) but inadequate sensitivity with high false-negative rates. The low sensitivity (<50%) shown in several studies is a critical public health concern, as asymptomatic or presymptomatic carriers may wrongly be assumed to be noninfectious, posing a significant risk of further spread in the community. Here, we show that the direct visual readout of SARS-CoV-2 LFDs is an inadequate approach to discriminate a potentially infective viral concentration in a biosample. We quantified significant immobilized antigen–antibody-labeled conjugate complexes within the LFDs visually scored as negative using high-sensitivity synchrotron X-ray fluorescence imaging. Correlating quantitative X-ray fluorescence measurements and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) determined numbers of viral copies, we identified that negatively scored samples could contain up to 100 PFU (equivalent here to ∼10 000 RNA copies/test). The study demonstrates where the shortcomings arise in many of the current direct-readout SARS-CoV-2 LFDs, namely, being a deficiency in the readout as opposed to the potential level of detection of the test, which is orders of magnitude higher. The present findings are of importance both to public health monitoring during the Coronavirus Disease 2019 (COVID-19) pandemic and to the rapid refinement of these tools for immediate and future applications.
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May 2021
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I16-Materials and Magnetism
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Diamond Proposal Number(s):
[15319]
Abstract: Objective: The structure of the polymer phase of dental resin-based-composites is highly sensitive to photo-polymerisation variables. The objective of this study was to understand how different polymer structures, generated with different photo-polymerisation protocols, respond to thermal perturbation. Methods: Experimental resins were prepared from a series of Bis-GMA/TEGDMA blends (40/60, 50/50 and 60/40 wt.%), with either Camphorquinone/DMAEMA or Lucirin TPO as the photo-initiator system. Resins were photo-polymerised, in a disc geometry, at either relatively ‘high’ (3000 mW cm−2 for 6 s) or ‘low’ (300 mW cm−2 for 60 s) irradiances ensuring matched radiant exposures (18 J cm−2). Specimens were heated, from 20−160 °C at a rate of 5 °C min−1, whilst simultaneous synchrotron X-ray scattering measurements were taken at 5 °C increments to determine changes in polymer chain segment extension and medium-range order as a function of temperature. For each unique resin composition (n = 3), differential scanning calorimetry was used to measure glass transition temperatures using the same heating protocol. A paired t-test was used to determine significant differences in the glass transition temperature between irradiance protocols and photo-initiator chemistry at ɑ = 0.05. Results: Resins pre-polymerised through the use of TPO and or high irradiances demonstrated a reduced rate of chain extension indicative of lower thermal expansion and a larger decrease in relative order when heated below the glass transition temperature. Above the transition temperature, differences in the rate of chain extension were negligible, but slower converted systems showed greater relative order. There was no significant difference in the glass transition temperature between different photo-initiator systems or irradiance protocols.
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Jan 2020
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I13-2-Diamond Manchester Imaging
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C. G.
Fenton
,
C. L.
Doig
,
S.
Fareed
,
A.
Naylor
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A. P.
Morrell
,
O.
Addison
,
C.
Wehmeyer
,
C. D.
Buckley
,
M. S.
Cooper
,
G. G.
Lavery
,
K.
Raza
,
R. S.
Hardy
Diamond Proposal Number(s):
[16654]
Open Access
Abstract: Background: Despite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11β-HSD1 to GIOP. Methods: Wild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR. Results: Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone. Conclusions: This study demonstrates that 11β-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11β-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids.
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Aug 2019
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I16-Materials and Magnetism
I22-Small angle scattering & Diffraction
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Diamond Proposal Number(s):
[11687, 14117, 15319]
Open Access
Abstract: The influence of reaction rate on the evolving polymer structure of photo-activated dimethacrylate biomedical resins was investigated using neutron and in situ synchrotron X-ray scattering with simultaneous Fourier-transform-near-infrared spectroscopy. Previous studies have correlated the degree of reactive group conversion with mechanical properties, but the impact of polymerization rate on the resultant polymer structure is unknown. Here, we demonstrate that the medium-range structural order at the functional end groups of these materials is dependent on the reaction rate. Accelerating polymerization increases correlation lengths in the methacrylate end groups but reduces the medium-range structural order per converted vinyl bond when compared with more slowly polymerized systems. At faster rates of polymerization, the conformation of atoms at the reacting end group can become fixed into the polymer structure at the onset of autodeceleration, storing residual strain. Neutron scattering confirms that the structural differences observed are reproduced at longer length scales. This effect is not as prominent in systems polymerized at slower rates despite similar final degrees of reactive group conversion. Results suggest that current interpretations of these materials, which extrapolate mechanical properties from conversion, may be incomplete. Accelerating polymerization can introduce structural differences, which will dictate residual strain and may ultimately explain the discrepancies in the predictive modeling of the mechanical behavior of these materials using conventional techniques.
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Jul 2019
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I14-Hard X-ray Nanoprobe
I18-Microfocus Spectroscopy
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Open Access
Abstract: Biological exposures to micro- and nano-scale exogenous metal particles generated as a consequence of in-service degradation of orthopaedic prosthetics can result in severe adverse tissues reactions. However, individual reactions are highly variable and are not easily predicted, due to in part a lack of understanding of the speciation of the metal-stimuli which dictates cellular interactions and toxicity. Investigating the chemistry of implant derived metallic particles in biological tissue samples is complicated by small feature sizes, low concentrations and often a heterogeneous speciation and distribution. These challenges were addressed by developing a multi-scale two-dimensional X-ray absorption spectroscopic (XAS) mapping approach to discriminate sub-micron changes in particulate chemistry within ex-vivo tissues associated with failed CoCrMo total hip replacements (THRs). As a result, in the context of THRs, we demonstrate much greater variation in Cr chemistry within tissues compared with previous reports. Cr compounds including phosphate, hydroxide, oxide, metal and organic complexes were observed and correlated with Co and Mo distributions. This variability may help explain the lack of agreement between biological responses observed in experimental exposure models and clinical outcomes. The multi-scale 2D XAS mapping approach presents an essential tool in discriminating the chemistry in dilute biological systems where speciation heterogeneity is expected.
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Jun 2019
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