Publications by year
2019
Meakin J, Ames RM, Jeynes JCG, Welsman JR, Gundry MJ, Knapp KM, Everson RM (2019). CitSeg pilot data.
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Jeynes JCG, Wordingham F, Moran LJ, Curnow A, Harries TJ (2019). Monte Carlo Simulations of Heat Deposition During Photothermal Skin Cancer Therapy Using Nanoparticles.
Biomolecules,
9(8).
Abstract:
Monte Carlo Simulations of Heat Deposition During Photothermal Skin Cancer Therapy Using Nanoparticles.
Photothermal therapy using nanoparticles is a promising new approach for the treatment of cancer. The principle is to utilise plasmonic nanoparticle light interaction for efficient heat conversion. However, there are many hurdles to overcome before it can be accepted in clinical practice. One issue is a current poor characterization of the thermal dose that is distributed over the tumour region and the surrounding normal tissue. Here, we use Monte Carlo simulations of photon radiative transfer through tissue and subsequent heat diffusion calculations, to model the spatial thermal dose in a skin cancer model. We validate our heat rise simulations against experimental data from the literature and estimate the concentration of nanorods in the tumor that are associated with the heat rise. We use the cumulative equivalent minutes at 43 °C (CEM43) metric to analyse the percentage cell kill across the tumour and the surrounding normal tissue. Overall, we show that computer simulations of photothermal therapy are an invaluable tool to fully characterize thermal dose within tumour and normal tissue.
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2018
Palombo F, Tamagnini F, Jeynes JCG, Mattana S, Swift I, Nallala J, Hancock J, Brown JT, Randall AD, Stone N, et al (2018). Detection of Aβ plaque-associated astrogliosis in Alzheimer’s disease brain by spectroscopic imaging and immunohistochemistry.
Analyst,
143, 850-857.
Abstract:
Detection of Aβ plaque-associated astrogliosis in Alzheimer’s disease brain by spectroscopic imaging and immunohistochemistry
Recent work using micro-Fourier transform infrared (μFTIR) imaging has revealed that a lipid-rich layer surrounds many plaques in post-mortem Alzheimer’s brain. However, the origin of this lipid layer is not known, nor is its role in the pathogenesis of Alzheimer’s disease (AD). Here, we studied the biochemistry of plaques in situ using a model of AD. We combined FTIR, Raman and immunofluorescence images, showing that astrocyte processes co-localise with the lipid ring surrounding many plaques. We used μFTIR imaging to rapidly measure chemical signatures of plaques over large fields of view, and selected plaques for higher resolution analysis with Raman microscopy. Raman maps showed similar lipid rings and dense protein cores as in FTIR images, but also revealed cell bodies. We confirmed the presence of plaques using amylo-glo staining, and detected astrocytes using immunohistochemistry, revealing astrocyte co-localisation with lipid rings. This work is important because it correlates biochemical changes surrounding the plaque with the biological process of astrogliosis.
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Tamagnini F, Cotton M, Goodall O, Harrison G, Jeynes C, Palombo F, Tomkow J, Tomkow T, Wedgwood K, Welsman J, et al (2018). ’Of Mice and Dementia’: a filmed conversation on the use of animals in dementia research.
Dementia (London, England),
17, 1055-1063.
Abstract:
’Of Mice and Dementia’: a filmed conversation on the use of animals in dementia research.
Preclinical science research focuses on the study of physiological systems regulating body functions, and how they are dysregulated in disease, in a non-human setting. For example, cells in a dish, computer simulations or animals. Scientific procedures traditionally involve a specialist scientist developing a hypothesis and subsequently testing it using an experimental set-up. The results are then disseminated to the wider scientific community, following peer review and only at the last stage the news will reach the general, lay public. In the last few years, some research funding institutions have promoted a different model, with the direct involvement of members of the public in the research co-creation, from the hypothesis development, to the grant revision, project monitoring and results communication. We personally experienced this model and brought it to a further level by producing a movie. Animal research is a very controversial topic as, while still being necessary for the investigation of body functions, it brings about issues related to the ethics, the regulation and the practical execution of experimental procedures on animals. Here we discuss the different stages of the ideation, production and outcomes of the movie ’Of Mice and Dementia’, a filmed conversation on animal experimentation in dementia research. The conversation was between scientists and lay people with a direct experience of dementia.
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2017
Jeynes JCG, Geraki K, Jeynes C, Zhaohong M, Bettiol AA, Latorre E, Harries LW, Soeller C (2017). Nanoscale Properties of Human Telomeres Measured with a Dual Purpose X-ray Fluorescence and Super Resolution Microscopy Gold Nanoparticle Probe.
ACS Nano,
11(12), 12632-12640.
Abstract:
Nanoscale Properties of Human Telomeres Measured with a Dual Purpose X-ray Fluorescence and Super Resolution Microscopy Gold Nanoparticle Probe.
Techniques to analyze human telomeres are imperative in studying the molecular mechanism of aging and related diseases. Two important aspects of telomeres are their length in DNA base pairs (bps) and their biophysical nanometer dimensions. However, there are currently no techniques that can simultaneously measure these quantities in individual cell nuclei. Here, we develop and evaluate a telomere "dual" gold nanoparticle-fluorescent probe simultaneously compatible with both X-ray fluorescence (XRF) and super resolution microscopy. We used silver enhancement to independently visualize the spatial locations of gold nanoparticles inside the nuclei, comparing to a standard QFISH (quantitative fluorescence in situ hybridization) probe, and showed good specificity at ∼90%. For sensitivity, we calculated telomere length based on a DNA/gold binding ratio using XRF and compared to quantitative polymerase chain reaction (qPCR) measurements. The sensitivity was low (∼10%), probably because of steric interference prohibiting the relatively large 10 nm gold nanoparticles access to DNA space. We then measured the biophysical characteristics of individual telomeres using super resolution microscopy. Telomeres that have an average length of ∼10 kbps, have diameters ranging between ∼60-300 nm. Further, we treated cells with a telomere-shortening drug and showed there was a small but significant difference in telomere diameter in drug-treated vs control cells. We discuss our results in relation to the current debate surrounding telomere compaction.
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Latorre E, Birar VC, Sheerin AN, Jeynes JCC, Hooper A, Dawe HR, Melzer D, Cox LS, Faragher RGA, Ostler EL, et al (2017). Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence.
BMC Cell Biol,
18(1).
Abstract:
Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence.
BACKGROUND: Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence. RESULTS: Treatment with resveralogues was associated with altered splicing factor expression and rescue of multiple features of senescence. This rescue was independent of cell cycle traverse and also independent of SIRT1, SASP modulation or senolysis. Under growth permissive conditions, cells demonstrating restored splicing factor expression also demonstrated increased telomere length, re-entered cell cycle and resumed proliferation. These phenomena were also influenced by ERK antagonists and agonists. CONCLUSIONS: This is the first demonstration that moderation of splicing factor levels is associated with reversal of cellular senescence in human primary fibroblasts. Small molecule modulators of such targets may therefore represent promising novel anti-degenerative therapies.
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2016
Georgantzoglou A, Merchant MJ, Jeynes JCG, Mayhead N, Punia N, Butler RE, Jena R (2016). Applications of high-throughput clonogenic survival assays in high-LET particle microbeams.
Frontiers in Oncology,
5(JAN).
Abstract:
Applications of high-throughput clonogenic survival assays in high-LET particle microbeams
© 2016 Georgantzoglou, Merchant, Jeynes, Mayhead, Punia, Butler and Jena. Charged particle therapy is increasingly becoming a valuable tool in cancer treatment, mainly due to the favorable interaction of particle radiation with matter. Its application is still limited due, in part, to lack of data regarding the radiosensitivity of certain cell lines to this radiation type, especially to high-linear energy transfer (LET) particles. From the earliest days of radiation biology, the clonogenic survival assay has been used to provide radiation response data. This method produces reliable data but it is not optimized for high-throughput microbeam studies with high-LET radiation where high levels of cell killing lead to a very low probability of maintaining cells' clonogenic potential. A new method, therefore, is proposed in this paper, which could potentially allow these experiments to be conducted in a high-throughput fashion. Cells are seeded in special polypropylene dishes and bright-field illumination provides cell visualization. Digital images are obtained and cell detection is applied based on corner detection, generating individual cell targets as x-y points. These points in the dish are then irradiated individually by a micron field size high-LET microbeam. Post-irradiation, time-lapse imaging follows cells' response. All irradiated cells are tracked by linking trajectories in all time-frames, based on finding their nearest position. Cell divisions are detected based on cell appearance and individual cell temporary corner density. The number of divisions anticipated is low due to the high probability of cell killing from high-LET irradiation. Survival curves are produced based on cell's capacity to divide at least four to five times. The process is repeated for a range of doses of radiation. Validation shows the efficiency of the proposed cell detection and tracking method in finding cell divisions.
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Jeynes JCG, Jeynes C, Palitsin V, Townley HE (2016). Direct quantification of rare earth doped titania nanoparticles in individual human cells.
NANOTECHNOLOGY,
27(28).
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2015
Georgantzoglou A, Merchant MJ, Jeynes JCG, Wera A-C, Kirkby KJ, Kirkby NF, Jena R (2015). Automatic cell detection in bright-field microscopy for microbeam irradiation studies.
PHYSICS IN MEDICINE AND BIOLOGY,
60(16), 6289-6303.
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Barazzuol L, Jeynes JCG, Merchant MJ, Wera A-C, Barry MA, Kirkby KJ, Suzuki M (2015). Radiosensitization of glioblastoma cells using a histone deacetylase inhibitor (SAHA) comparing carbon ions with X-rays.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY,
91(1), 90-98.
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2014
Mohamad AS, Jeynes JCG, Hughes MP (2014). Dielectrophoretic Response of DNA Shows Different Conduction Mechanisms for Poly(dG)-Poly(dC) and Poly(dA)-Poly(dT) in Solution.
IEEE TRANSACTIONS ON NANOBIOSCIENCE,
13(1), 51-54.
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Wera A-C, Barazzuol L, Jeynes JCG, Merchant MJ, Suzuki M, Kirkby KJ (2014). Influence of the nucleus area distribution on the survival fraction after charged particles broad beam irradiation.
PHYSICS IN MEDICINE AND BIOLOGY,
59(15), 4197-4211.
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Jeynes JCG, Merchant MJ, Spindler A, Wera A-C, Kirkby KJ (2014). Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies.
PHYSICS IN MEDICINE AND BIOLOGY,
59(21), 6431-6443.
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2013
Jeynes JCG, Merchant MJ, Barazzuol L, Barry M, Guest D, Palitsin VV, Grime GW, Tullis IDC, Barber PR, Vojnovic B, et al (2013). "Broadbeam" irradiation of mammalian cells using a vertical microbeam facility.
RADIATION AND ENVIRONMENTAL BIOPHYSICS,
52(4), 513-521.
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Barazzuol L, Jena R, Burnet NG, Meira LB, Jeynes JCG, Kirkby KJ, Kirkby NF (2013). Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma.
RADIATION ONCOLOGY,
8 Author URL.
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Kar S, Doria D, Kakolee KF, Prasad R, Litt S, Ahmed H, Nersisyan G, Lewis C, Zepf M, Borghesi M, et al (2013). First Results on Cell Irradiation with laser-driven protons on the TARANIS system.
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Prakrajang K, Jeynes JCG, Merchant MJ, Kirkby K, Kirkby N, Thopan P, Yu LD (2013). MeV single-ion beam irradiation of mammalian cells using the Surrey vertical nanobeam, compared with broad proton beam and X-ray irradiations.
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Jeynes JCG, Jeynes C, Merchant MJ, Kirkby KJ (2013). Measuring and modelling cell-to-cell variation in uptake of gold nanoparticles.
ANALYST,
138(23), 7070-7074.
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Hanton F, Doria D, Kakolee KF, Kar S, Litt SK, Fiorini F, Ahmed H, Green S, Jeynes JCG, Kavanagh J, et al (2013). Radiobiology at ultra-high dose rates employing laser-driven ions.
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2012
Merchant MJ, Jeynes JCG, Grime GW, Palitsin V, Tullis IDW, Barber PR, Vojnovic B, Webb RP, Kirkby KJ (2012). A Focused Scanning Vertical Beam for Charged Particle Irradiation of Living Cells with Single Counted Particles.
RADIATION RESEARCH,
178(3), 182-190.
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Doria D, Kakolee KF, Kar S, Litt SK, Fiorini F, Ahmed H, Green S, Jeynes JCG, Kavanagh J, Kirby D, et al (2012). Biological Cell Irradiation at Ultrahigh Dose Rate Employing Laser Driven Protons.
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Doria D, Kakolee KF, Kar S, Litt SK, Fiorini F, Ahmed H, Green S, Jeynes JCG, Kavanagh J, Kirby D, et al (2012). Biological effectiveness on live cells of laser driven protons at dose rates exceeding 10(9) Gy/s.
AIP ADVANCES,
2(1).
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Barazzuol L, Jena R, Burnet NG, Jeynes JCG, Merchant MJ, Kirkby KJ, Kirkby NF (2012). In Vitro Evaluation of Combined Temozolomide and Radiotherapy Using X Rays and High-Linear Energy Transfer Radiation for Glioblastoma.
RADIATION RESEARCH,
177(5), 651-662.
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2011
Fiorini F, Kirby D, Borghesi M, Doria D, Jeynes JCG, Kakolee KF, Kar S, Kaur S, Kirby KJ, Merchant MJ, et al (2011). Dosimetry and spectral analysis of a radiobiological experiment using laser-driven proton beams.
PHYSICS IN MEDICINE AND BIOLOGY,
56(21), 6969-6982.
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2010
Jeynes JCG, Bailey MJ, Coley H, Kirkby KJ, Jeynes C (2010). Microbeam PIXE analysis of platinum resistant and sensitive ovarian cancer cells.
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2009
Jeynes JCG, Webb M, Kirkby KJ, Kirkby NF, Bradley DA (2009). Proceedings of the First International Conference on Biomedical Applications of High Energy Ion Beams Preface.
APPLIED RADIATION AND ISOTOPES,
67(3), 369-370.
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2008
Jeynes JCG, Jeynes C, Kirkby KJ, Ruemmeli A, Silva SRP (2008). RBS/EBS/PIXE measurement of single-walled carbon nanotube modification by nitric acid purification treatment.
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2006
Jeynes JCG, Mendoza E, Chow DCS, Watts PCR, McFadden J, Silva SRP (2006). Generation of chemically unmodified pure single-walled carbon nanotubes by solubilizing with RNA and treatment with ribonuclease A.
ADVANCED MATERIALS,
18(12), 1598-+.
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2005
Jeynes JCG, Mendoza E, Chow D, McFadden J, Silva SRP (2005). DNA/RNA purified single walled carbon nanotubes on self-assembled networks.
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DNA/RNA purified single walled carbon nanotubes on self-assembled networks
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Newcombe J, Jeynes JC, Mendoza E, Hinds J, Marsden GL, Stabler RA, Marti M, McFadden JJ (2005). Phenotypic and transcriptional characterization of the meningococcal PhoPQ system, a magnesium-sensing two-component regulatory system that controls genes involved in remodeling the meningococcal cell surface.
J Bacteriol,
187(14), 4967-4975.
Abstract:
Phenotypic and transcriptional characterization of the meningococcal PhoPQ system, a magnesium-sensing two-component regulatory system that controls genes involved in remodeling the meningococcal cell surface.
We previously identified and characterized a two-component regulatory system in the meningococcus with homology to the phoP-phoQ system in salmonella and showed that allele replacement of the NMB0595 regulator gene led to loss of virulence, sensitivity to antimicrobial peptides, perturbed protein expression, and magnesium-sensitive growth. On the basis of these findings we proposed that the system should be designated the meningococcal PhoPQ system. Here we further characterized the NMB0595 mutant and demonstrated that it had increased membrane permeability and was unable to form colonies on solid media with low magnesium concentrations, features that are consistent with disruption of PhoPQ-mediated modifications to the lipooligosaccharide structure. We examined the transcriptional profiles of wild-type and NMB0595 mutant strains and found that magnesium-regulated changes in gene expression are completely abrogated in the mutant, indicating that, similar to the salmonella PhoPQ system, the meningococcal PhoPQ system is regulated by magnesium. Transcriptional profiling of the mutant indicated that, also similar to the salmonella PhoPQ system, the meningococcal system is involved in control of virulence and remodeling of the bacterial cell surface in response to the host environment. The results are consistent with the hypothesis that the PhoP homologue plays a role in the meningococcus similar to the role played by PhoP in salmonella. Elucidating the role that the PhoPQ system and PhoPQ-regulated genes play in the response of the meningococcus to the host environment may provide new insights into the pathogenic process.
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