269 results on '"Martin, Francis L"'
Search Results
2. List of contributors
- Author
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Alvarez-Puebla, Ramon A., primary, Baker, Matthew J., additional, Baranska, Malgorzata, additional, Beattie, James W., additional, Bik, Ewelina, additional, Bonnier, Franck, additional, Bouř, Petr, additional, Bruno, Clément, additional, Butler, Holly J., additional, Byrne, Bernadette, additional, Byrne, Hugh J., additional, Cameron, James M., additional, Chrabaszcz, Karolina, additional, Czamara, Krzysztof, additional, Dorosz, Aleksandra, additional, Dybas, Jakub, additional, Guerrini, Luca, additional, Handen, Joseph, additional, Hudecová, Jana, additional, Ishigaki, Mika, additional, Iwasaki, Keita, additional, Jung, Young Mee, additional, Kandori, Hideki, additional, Katayama, Kota, additional, Kazarian, Sergei G., additional, Kneipp, Janina, additional, Kochan, Kamila, additional, Lednev, Igor K., additional, Lendl, Bernhard, additional, Lima, Kássio M.G., additional, Lipiec, Ewelina, additional, Majzner, Katarzyna, additional, Malek, Kamilla, additional, Martin, Francis L., additional, Marzec, Katarzyna M., additional, Miller, Lisa M., additional, Mizutani, Yasuhisa, additional, Morais, Camilo L.M., additional, Noda, Isao, additional, Noothalapati, Hemanth, additional, Ozaki, Yukihiro, additional, Pacia, Marta Z., additional, Pan, Zhijun, additional, Parachalil, Drishya Rajan, additional, Park, Yeonju, additional, Santos, Marfran C.D., additional, Schlücker, Sebastian, additional, Schwaighofer, Andreas, additional, Song, Cai Li, additional, Wang, Yuling, additional, Wiercigroch, Ewelina, additional, Wislocka, Adrianna, additional, Wood, Bayden R., additional, Yamamoto, Tatsuyuki, additional, Zhang, Yuying, additional, and Zhuang, Wei, additional
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- 2020
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3. Biospectroscopy for Plant and Crop Science
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Skolik, Paul, primary, McAinsh, Martin R., additional, and Martin, Francis L., additional
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- 2018
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4. Direct identification and visualisation of real-world contaminating microplastics using Raman spectral mapping with multivariate curve resolution-alternating least squares
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Tian, Meiping, Medeiros-De-morais, Camilo De lelis, Shen, Heqing, Pang, Weiyi, Xu, Li, Huang, Qingyu, Martin, Francis L, Tian, Meiping, Medeiros-De-morais, Camilo De lelis, Shen, Heqing, Pang, Weiyi, Xu, Li, Huang, Qingyu, and Martin, Francis L
- Abstract
Microplastics (MPs) contamination is ubiquitous in environmental matrices worldwide. Moreover these pollutants can be ingested by organisms and transported to organs via the circulatory system. Although efficient methods for the analysis of MPs derived from environment matrices and organisms' tissue samples have been developed after special sample pre-treatment, there remains a need for an optimised approach allowing direct identification and visualisation these MPs in real environmental matrices and organismal samples. Herein, we firstly used a multivariate curve resolution-alternating least squares (MCR-ALS) analysis of Raman hyperspectral imaging data to direct identification and visualisation of MPs in a complex serum background. Four common MPs types including polyethylene (PE), polystyrene (PS), polypropylene (PP) and polyethylene terephthalate (PET) were identified and visualised either individually or in mixtures within spiked samples at an 8-μm spatial resolution. Moreover, Raman imaging based on MCR-ALS was successfully applied in fish faeces biological samples and environmental sand samples for in situ MPs identification directly without washing or removal of organic matter. The current results demonstrate Raman imaging based on MCR-ALS as a novel imaging approach for direct identification and visualisation of MPs, through extraction of MPs' chemical spectra within a complicated biological or environmental background whilst eliminating overlapping Raman bands and fluorescence interference. [Abstract copyright: Copyright © 2021 Elsevier B.V. All rights reserved.]
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- 2022
5. Raman hyperspectral imaging coupled to three-dimensional discriminant analysis: classification of meningiomas brain tumour grades
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Lilo, Taha Luay, Medeiros-De-morais, Camilo De lelis, Ashton, Katherine M., Davis, Charles, Dawson, Timothy P., Martin, Francis L., Alder, Jane Elizabeth, Roberts, Gareth, Ray, Arup, Gurusinghe, Nihal, Lilo, Taha Luay, Medeiros-De-morais, Camilo De lelis, Ashton, Katherine M., Davis, Charles, Dawson, Timothy P., Martin, Francis L., Alder, Jane Elizabeth, Roberts, Gareth, Ray, Arup, and Gurusinghe, Nihal
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Meningiomas remains a clinical dilemma. They are the commonest “benign” types of brain tumours and, although being typically benign, they are divided into three WHO grades categories (I, II and III) which are associated with the tumour growth rate and likelihood of recurrence. Recurrence depends on extend of surgery as well as histopathological diagnosis. There is a marked variation amongst surgeons in the follow-up arrangements for their patients even within the same unit which has a significant clinical, and financial implication. Knowing the tumour grade rapidly is an important factor to predict surgical outcomes and adequate patient treatment. Clinical follow up sometimes is haphazard and not based on clear evidence. Spectrochemical techniques are a powerful tool for cancer diagnostics. Raman hyperspectral imaging is able to generate spatially-distributed spectrochemical signatures with great sensitivity. Using this technique, 95 brain tissue samples (66 meningiomas WHO grade I, 24 meningiomas WHO grade II and 5 meningiomas that reoccurred) were analysed in order to discriminate grade I and grade II samples. Newly-developed three-dimensional discriminant analysis algorithms were used to process the hyperspectral imaging data in a 3D fashion. Three-dimensional principal component analysis quadratic discriminant analysis (3D-PCA-QDA) was able to distinguish grade I and grade II meningioma samples with 96% test accuracy (100% sensitivity and 95% specificity). This technique is here shown to be a high-throughput, reagent-free, non-destructive, and can give accurate predictive information regarding the meningioma tumour grade, hence, having enormous clinical potential with regards to being developed for intra-operative real-time assessment of disease.
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- 2022
6. Diagnostic segregation of human breast tumours using Fourier-transform infrared spectroscopy coupled with multivariate analysis: Classifying cancer subtypes
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Luo, Youhong, Liu, Hui, Wu, Chunye, Paraskevaidi, Maria, Deng, Yujie, Shi, Wenjie, Yuan, Ye, Feng, Ruifa, Martin, Francis L, Pang, Weiyi, Luo, Youhong, Liu, Hui, Wu, Chunye, Paraskevaidi, Maria, Deng, Yujie, Shi, Wenjie, Yuan, Ye, Feng, Ruifa, Martin, Francis L, and Pang, Weiyi
- Abstract
The present study aimed to investigate whether attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy coupled with multivariate analysis could be applied to discriminate and classify among breast tumour molecular subtypes based on the unique spectral "fingerprints" of their biochemical composition. The different breast cancer tissues and normal breast tissues were collected and identified by pathology and ATR-FTIR spectroscopy respectively. The study indicates that the levels of the lipid-to-protein, nucleic acid-to-lipid, phosphate-to-carbohydrate and their secondary structure ratio, including RNA-to-DNA, Amide I-to-Amide II, and RNA-to-lipid ratios were significantly altered among the molecular subtype of breast tumour compared with normal breast tissues, which helps explain the changes in the biochemical structure of different molecular phenotypes of breast cancer. Tentatively-assigned characteristic peak ratios of infrared (IR) spectra reflect the changes of the macromolecule structure in different issues to a great extent and can be used as a potential biomarker to predict the molecular subtype of breast tumour. The present study acts as the first case study to show the successful application of IR spectroscopy in classifying subtypes of breast cancer with biochemical alterations. Therefore, the present study is likely to help to provide a new diagnostic approach for the accurate diagnosis of breast tumours and differential molecular subtypes and has the potential to be used for further intraoperative management. [Abstract copyright: Copyright © 2021 Elsevier B.V. All rights reserved.]
- Published
- 2021
7. Attenuated Total Reflection Fourier-Transform Infrared Spectroscopy Coupled with Chemometrics Directly Detects Pre- and Post-Symptomatic Changes in Tomato Plants Infected with Botrytis cinerea
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Skolik, Paul, Medeiros-De-morais, Camilo De lelis, Martin, Francis L., McAinsh, Martin R., Skolik, Paul, Medeiros-De-morais, Camilo De lelis, Martin, Francis L., and McAinsh, Martin R.
- Abstract
Sensor-based detection of pests and pathogens in a high throughput and non-destructive manner is essential for mitigating crop loss. Infrared (IR) sensors in the form of vibrational spectroscopy provide both biochemical information about disease, as well as a large number of variables for chemometrics. This approach is highly adaptable to most biological systems including interactions between plants and their environments. Fast-acting necrotrophic fungal pathogens present a specific group of pests with adverse effects on food production and supply and are therefore pertinent to food security. Botrytis cinerea and Solanum lycopersicum are models for the study of fungal and crop biology respectively. Herein we use a compact mid-IR spectrometer with attenuated total reflection (ATR) attachment to measure the plant-microbe interaction between S. lycopersicum and B. cinerea on leaves, in vivo of intact plants. Chemometric models including exploratory principal component analysis (PCA) solely, and as a classifier in combination with linear discriminant analysis (PCA-LDA) are applied. Fingerprint spectra (1800-900 cm-1) were excellent discriminators of plant disease in both visually symptomatic as well pre-symptomatic plants. Major biochemical alterations in leaf tissue as a result of infection are discussed. Diagnostic potential for automatic decision-making platforms is shown by high accuracy rates of 100% for detecting plant disease at various stages of progression.
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- 2020
8. Discrimination of oesophageal transformation stages to adenocarcinoma in human tissue samples using Raman microspectroscopy
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Maitra, Ishaan, Medeiros-De-morais, Camilo De lelis, Lima, Kassio M.G., Ashton, Katherine M., Bury, Danielle, Date, Ravindra S., Martin, Francis L., Maitra, Ishaan, Medeiros-De-morais, Camilo De lelis, Lima, Kassio M.G., Ashton, Katherine M., Bury, Danielle, Date, Ravindra S., and Martin, Francis L.
- Abstract
The gold standard for diagnosis of oesophageal adenocarcinoma still requires histological examination of mucosal biopsies obtained at oesophagogastroduodenoscopy. Herein, Raman spectral analysis of ex vivo oesophageal tissue was performed, including all classifications to oesophageal adenocarcinoma. This study adds further validation to previous human oesophageal tissue studies identifying the potential for Raman spectroscopy in differentiating between all classes in oesophageal transformation to oesophageal adenocarcinoma [normal; inflammatory; Barrett’s oesophagus; low-grade dysplasia; high-grade dysplasia; and, oesophageal adenocarcinoma]. Tissue spectra were analysed using principal component analysis-quadratic discriminant analysis (PCA-QDA), successive projections algorithm-quadratic discriminant analysis or genetic algorithm-quadratic discriminant analysis. The variables selected were then used for discriminating the tissue classes based on the unique spectral "fingerprints" of their biochemical composition. Accuracy tests including sensitivity and specificity were determined. The best model using PCA-QDA successfully classified normal, inflammatory, Barrett’s oesophagus, low-grade dysplasia, high-grade dysplasia and oesophageal adenocarcinoma tissues with 91%–100% accuracy, 90%-100% sensitivity, and 71%–100% specificity. Amongst the main distinguishing features in the pre-processed Raman spectra, the wavenumbers at 1296 cm-1 (CH2 deformation), 1448 cm-1 (CH2/CH3 deformation) and 1668 cm−1 (Amide I) were found to increase in amplitude with increasing differentiation. Raman spectroscopy exhibits promise in distinguishing the stages leading to oesophageal adenocarcinoma and may play a role in surveillance programs in premalignant conditions such as Barrett’s oesophagus.
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- 2020
9. Gene-environment interactions between GSTs polymorphisms and targeted epigenetic alterations in hepatocellular carcinoma following organochlorine pesticides (OCPs) exposure
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Tian, Meiping, Zhao, Benhua, Martin, Francis L, Medeiros-De-morais, Camilo De lelis, Liu, Liangpo, Huang, Qingyu, Zhang, Jie, Shen, Heqing, Tian, Meiping, Zhao, Benhua, Martin, Francis L, Medeiros-De-morais, Camilo De lelis, Liu, Liangpo, Huang, Qingyu, Zhang, Jie, and Shen, Heqing
- Abstract
Exposure to environmental pollutant organochlorine pesticides (OCPs) and the role of tumour suppressor GSTs gene polymorphisms as well as epigenetic alterations have all been well reported in hepatocarcinogenesis. However, the interplay between environmental risk factors and polymorphic tumour suppressor genes or epigenetic factors in hepatocellular carcinoma (HCC) development remains ambiguous. Herein, we investigated the relationship of three GSTs polymorphisms (GSTT1 deletion, GSTM1 deletion, GSTP1 rs1695) as well as GSTP1 promoter region DNA methylation and HCC risk with a particular focus on the interaction with OCPs exposure among 90 HCC cases and 99 controls in a Chinese population. Serum samples were analysed for OCPs exposure employing gas chromatography coupled with mass selective detector (GC-MS). GSTs polymorphisms and epigenetic alterations were determined using high-resolution melting PCR (HRM PCR) and DNA sequencing. After adjusting for confounders (HBV infection, smoking, alcohol consumption, BMI, age, gender), OCPs exposure and GSTP1 methylation is significantly associated with elevated risk of HCC, while no significance is observed for GSTs polymorphisms. Moreover, the effects of OCPs exposure on HCC risk are more pronounced amongst GSTP1 (Ile/Val + Val/Val) and GSTP1 promoter methylation subjects than those who were GSTP1 (Ile/Ile) and unmethylated subjects. The interactions between OCPs exposure and GSTP1 genotype as well as GSTP1 epigenetic status are statistically significant. The current study demonstrates the importance of gene-environment interactions in the multifactorial development of HCC. [Abstract copyright: Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.]
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- 2020
10. Phthalate side side-chain structures and hydrolysis metabolism associated with steroidogenic effects in MLTC-1 Leydig cells
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Tian, Meiping, Zhang, Xi, Martin, Francis L, Wang, Heng, Zhang, Jie, Huang, Qingyu, Wang, Xiaofei, Shen, Heqing, Tian, Meiping, Zhang, Xi, Martin, Francis L, Wang, Heng, Zhang, Jie, Huang, Qingyu, Wang, Xiaofei, and Shen, Heqing
- Abstract
Although it is well acknowledged that the anti-androgenic phthalate diesters can be readily hydrolysed into their monoester counterparts, their metabolites’ toxicology remains obscure. Herein, we tested the hypothesis that hydrolysis of one of the two ester bonds can mediate phthalate diesters’ potential endocrine effects in MLTC-1 Leydig cells, in line with their ability to disrupt androgen secretion in humans. Five diesters (DMP, DEP, DBP, DBzP and DEHP) and five monoesters (MMP, MEP, MBP, MBzP and MEHP) phthalates as mixtures or individually were applied to cell lines to investigate differences in phthalates’ hydrolysis associated with varying side-chain structures and steroidogenic effects. Short-chain diesters DMP, DEP and DBP are more readily hydrolysed compared to the long-chain DEHP, while aromatic alkyl chain DBzP cannot be metabolized completely in vitro. When the hydrolysis processes are interrupted, the diester phthalates’ steroidogenic effects can be influenced via regulating related steroidogenic pathway genes. With 10 to 100 μM treatment exposures, androgenic effects were observed only with DMP or DEP but not for MMP or MEP; while the phthalate diesters DBP, DBzP or DEHP generally exhibited more complex steroidogenic effects than their corresponding monoester counterparts (i.e., biphasic androgen and anti-androgen effects for diesters but monotonic androgen effects for monoesters were observed). DBP elicited hydrolysis-related steroidogenic modulation, in which the anti-androgenic effects of diester DBP reversed into the androgenic effects of monoester MBP at 100 μM. Phthalate metabolites appear to exert different effects at an endocrine level compared to parent compounds, and deeper insights into how the hydrolytic process is related to this alternating toxicity would improve our understanding of a risk assessment for these widespread contaminants in male reproduction.
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- 2019
11. Biphasic effects of perfluorooctanoic acid on steroidogenesis in mouse Leydig tumour cells
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Tian, Meiping, Huang, Qingyu, Wang, Heng, Martin, Francis L, Liu, Liangpo, Zhang, Jie, Shen, Heqing, Tian, Meiping, Huang, Qingyu, Wang, Heng, Martin, Francis L, Liu, Liangpo, Zhang, Jie, and Shen, Heqing
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Perfluorooctanoic acid (PFOA) is a persistent organic pollutant, which may possess endocrine disrupting properties. Herein, we investigated the possible mechanism(s) of toxicity and steroidogenesis in mouse Leydig cells. MLTC-1 (mouse Leydig tumour cells) cells were exposed to 0, 50, 100 or 200 μM PFOA for 48 h to ascertain their effects on the nuclear (membrane) receptor responses, steroidogenesis pathway and related regulated gene expression and steroid hormone secretion profiles. Our results reveal that nuclear receptors PXR, SR-B1 and LHR are sensitive to PFOA exposure. PFOA can accumulate in mitochondria and alter cholesterol precursor (fatty acid) mitochondrial transport process-related gene expression and thus inhibit steroid hormone precursor (cholesterol) production. In particular, PFOA exhibits biphasic effects on testosterone and progesterone production at differing levels of exposure. These findings indicate the potential endocrine-related effects of PFOA on steroid hormone secretion in Leydig cells and point to a novel disruption model. [Abstract copyright: Copyright © 2018 Elsevier Inc. All rights reserved.]
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- 2019
12. 4-Nonylphenol effects on rat testis and sertoli cells determined by spectrochemical techniques coupled with chemometric analysis
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Duan, Peng, Liu, Bisen, Medeiros-De-morais, Camilo De lelis, Zhao, Jing, Li, Xiandong, Tu, Jian, Yang, Weiyingxue, Chen, Chunling, Long, Manman, Feng, Xiaobing, Martin, Francis L, Xiong, Chengliang, Duan, Peng, Liu, Bisen, Medeiros-De-morais, Camilo De lelis, Zhao, Jing, Li, Xiandong, Tu, Jian, Yang, Weiyingxue, Chen, Chunling, Long, Manman, Feng, Xiaobing, Martin, Francis L, and Xiong, Chengliang
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Herein, vibrational spectroscopy has been applied for qualitative identification of biomolecular alterations that occur in cells and tissues following chemical treatment. Towards this end, we combined attenuated total reflection Fourier-transform infrared (ATR-FTIR) and Raman spectroscopy to assess testicular toxicology after 4-nonylphenol (NP) exposure, an estrogenic endocrine disruptor affecting testicular function in rats and other species. Rats aged 21, 35 or 50 days received NP at intra-peritoneal doses of 0, 25, 50 or 100 mg/kg for 20 consecutive days. Primary Sertoli cells (SCs) were treated with NP at various concentrations (0, 2.5, 5, 10 or 20 μM) for 12 h. Post-exposure, testicular cells, interstitial tissue and SCs were interrogated respectively using spectrochemical techniques coupled with multivariate analysis. Distinct biomolecular segregation between the NP-exposed samples vs. control were observed based on infrared (IR) spectral regions of 3200–2800 cm−1 and 1800-900 cm−1, and the Raman spectral region of 1800–900 cm−1. For in vivo experiments, the main wavenumbers responsible for segregation varied significantly among the three age classes. The main IR and Raman band differences between NP-exposed and control groups were observed for Amide (proteins), lipids and DNA/RNA. An interesting finding was that the peptide aggregation level, Amide Ӏ-to-Amide II ratio, and phosphate-to-carbohydrate ratio were considerably reduced in ex vivo NP-exposed testicular cells or SCs in vitro. This study demonstrates that ATR-FTIR and Raman spectroscopy techniques can be applied towards analysing NP-induced testicular biomolecular alterations.
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- 2019
13. A human-derived prostate co-culture microtissue model using epithelial (RWPE-1) and stromal (WPMY-1) cell lines
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Dent, Matthew P., Madnick, Samantha J., Policelli, Marguerite Vantangoli, Bars, Chloe, Li, Hui, Amin, Ali, Carmichael, Paul L., Martin, Francis L, Boekelheide, Kim, Dent, Matthew P., Madnick, Samantha J., Policelli, Marguerite Vantangoli, Bars, Chloe, Li, Hui, Amin, Ali, Carmichael, Paul L., Martin, Francis L, and Boekelheide, Kim
- Abstract
The development and normal function of prostate tissue depends on signalling interactions between stromal and epithelial compartments. Development of a prostate microtissue composed of these two components can help identify substance exposures that could cause adverse effects in humans as part of a non-animal risk assessment. In this study, prostate microtissues composed of human derived stromal (WPMY-1) and epithelial (RWPE-1) cell lines grown in scaffold-free hydrogels were developed and characterized using immunohistochemistry, light microscopy, and qRT-PCR. Within 5 days after seeding, the microtissues self-organized into spheroids consisting of a core of stromal WPMY-1 cells surrounded by epithelial RWPE-1 cells. The RWPE-1 layer is reflective of intermediate prostatic epithelium, expressing both characteristics of the luminal (high expression of PSA) and basal (high expression of cytokeratins 5/6 and 14) epithelial cells. The response of the microtissues to an androgen (dihydrotestosterone, DHT) and an anti-androgen (flutamide) was also investigated. Treatment with DHT, flutamide or a mixture of DHT and flutamide indicated that the morphology and self-organization of the microtissues is androgen dependent. qRT-PCR data showed that a saturating concentration of DHT increased the expression of genes coding for the estrogen receptors (ESR1 and ESR2) and decreased the expression of CYP1B1 without affecting the expression of the androgen receptor. With further development and optimization RWPE-1/WPMY-1 microtissues can play an important role in non-animal risk assessments.
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- 2019
14. TTWD-DA: A MATLAB toolbox for discriminant analysis based on trilinear three-way data
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Medeiros-De-morais, Camilo De lelis, Lima, Kassio M.G., Martin, Francis L, Medeiros-De-morais, Camilo De lelis, Lima, Kassio M.G., and Martin, Francis L
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Three-way trilinear data is increasingly used in chemical and biochemical applications. This type of data is composed of three-way structures representing two different signal responses and one sample dimension distributed among a 3D structure, such as the data represented by fluorescence excitation emission matrices (EMMs), spectral-pH responses, spectral-kinetic responses, spectral-electric potential responses, among others. Herein, we describe a new MATLAB toolbox for classification of trilinear three-way data using discriminant analysis techniques (linear discriminant analysis [LDA], quadratic discriminant analysis [QDA], and partial least squares discriminant analysis [PLS-DA]), termed “TTWD-DA”. These discrimination techniques were coupled to multivariate deconvolution techniques by means of parallel factor analysis (PARAFAC) and Tucker3 algorithm. The toolbox is based on a user-friendly graphical interface, where these algorithms can be easily applied. Also, as output, multiple figures of merit are automatically calculated, such as accuracy, sensitivity and specificity. This software is free available online.
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- 2019
15. Phages Enter the Fight against Colorectal Cancer
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Kannen, Vinicius, Parry, Lee, Martin, Francis L, Kannen, Vinicius, Parry, Lee, and Martin, Francis L
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Intestinal microbiota undergo significant changes in colorectal cancer (CRC). Zheng et al. (Nat. Biomed. Eng., 2019) observe detrimental overpopulation of Fusobacterium nucleatum in mice and patients, suppressing the beneficial butyrate-producing Clostridium butyricum. Phage-guided irinotecan-loaded dextran nanoparticles promote release of bacterial-derived butyrate, while F. nucleatum and CRC cells are eliminated. These findings describe a possible novel therapeutic strategy for CRC. [Abstract copyright: Copyright © 2019 Elsevier Inc. All rights reserved.]
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- 2019
16. Identifying spectral markers for the differential diagnosis of dementia in biofluids and buccal cells
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Paraskevaidi, Maria, Medeiros-De-morais, Camilo De lelis, Crean, Stjohn, Martin, Francis L, Paraskevaidi, Maria, Medeiros-De-morais, Camilo De lelis, Crean, Stjohn, and Martin, Francis L
- Abstract
Background Estimates of dementia prevalence have shown that 46.8 million people live with the condition worldwide and this is expected to reach 75 million by 2030 (Prince, 2015). Even though these diseases are becoming widely common, there is currently no disease-modifying therapy or at least a definitive diagnostic test that would allow for an early detection (Mangialasche et al., 2010). It is anticipated that preventative and therapeutic strategies will be more efficient in individuals with the disease at a very early stage, before extensive brain damage occurs (Sperling et al., 2011). Vibrational spectroscopic methods generate a characteristic fingerprint of a sample’s status, investigating many biomolecules, such as lipids, proteins and nucleic acids, which is of huge importance when dealing with multifactorial diseases. Previous studies have demonstrated spectroscopy’s ability to detect Alzheimer’s disease (AD) in blood samples (Paraskevaidi et al., 2017; Paraskevaidi et al., 2018a; Paraskevaidi et al., 2018b). Changes related to dementia have been shown to be reflected in the blood circulation as well as other peripheral cell sources. Buccal cells have shown to reflect changes in the brain and have been studied as potential biomarkers for AD and mild cognitive impairment (Francois et al., 2014). Methods We have used spectroscopic techniques to detect patients with early- and late-stage dementia. We have correlated the spectral data with relevant clinical and non-clinical information (e.g., age, gender, ethnicity and oral hygiene) and calculated the diagnostic accuracy of the test. Recruitment of more participants is on-going. Buccal swabs are collected to provide a completely non-invasive sampling method. Results Accurate segregation between dementing patients and healthy controls has been achieved with high diagnostic accuracy (up to 95%). Spectral markers of disease have been identified. Conclusions Our preliminary results show that spectroscopy holds great
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- 2019
17. Uncertainty estimation and misclassification probability for classification models based on discriminant analysis and support vector machines
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Medeiros-De-morais, Camilo De lelis, Lima, Kassio M.G., Martin, Francis L, Medeiros-De-morais, Camilo De lelis, Lima, Kassio M.G., and Martin, Francis L
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Uncertainty estimation provides a quantitative value of the predictive performance of a classification model based on its misclassification probability. Low misclassification probabilities are associated with a low degree of uncertainty, indicating high trustworthiness; while high misclassification probabilities are associated with a high degree of uncertainty, indicating a high susceptibility to generate incorrect classification. Herein, misclassification probability estimations based on uncertainty estimation by bootstrap were developed for classification models using discriminant analysis [linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA)] and support vector machines (SVM). Principal component analysis (PCA) was used as variable reduction technique prior classification. Four spectral datasets were tested (1 simulated and 3 real applications) for binary and ternary classifications. Models with lower misclassification probabilities were more stable when the spectra were perturbed with white Gaussian noise, indicating better robustness. Thus, misclassification probability can be used as an additional figure of merit to assess model robustness, providing a reliable metric to evaluate the predictive performance of a classifier.
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- 2019
18. Raman spectroscopic techniques to detect ovarian cancer biomarkers in blood plasma
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Paraskevaidi, Maria, Ashton, Katherine M, Stringfellow, Helen F, Wood, Nicholas J, Keating, Patrick J, Rowbottom, Anthony W, Martin-Hirsch, Pierre L, Martin, Francis L, Paraskevaidi, Maria, Ashton, Katherine M, Stringfellow, Helen F, Wood, Nicholas J, Keating, Patrick J, Rowbottom, Anthony W, Martin-Hirsch, Pierre L, and Martin, Francis L
- Abstract
Robust diagnosis of ovarian cancer is crucial to improve patient outcomes. The lack of a single and accurate diagnostic approach necessitates the advent of novel methods in the field. In the present study, two spectroscopic techniques, Raman and surface-enhanced Raman spectroscopy (SERS) using silver nanoparticles, have been employed to identify signatures linked to cancer in blood. Blood plasma samples were collected from 27 patients with ovarian cancer and 28 with benign gynecological conditions, the majority of which had a prolapse. Early ovarian cancer cases were also included in the cohort (n = 17). The derived information was processed to account for differences between cancerous and healthy individuals and a support vector machine (SVM) algorithm was applied for classification. A subgroup analysis using CA-125 levels was also conducted to rule out that the observed segregation was due to CA-125 differences between patients and controls. Both techniques provided satisfactory diagnostic accuracy for the detection of ovarian cancer, with spontaneous Raman achieving 94% sensitivity and 96% specificity and SERS 87% sensitivity and 89% specificity. For early ovarian cancer, Raman achieved sensitivity and specificity of 93% and 97%, respectively, while SERS had 80% sensitivity and 94% specificity. Five spectral biomarkers were detected by both techniques and could be utilised as a panel of markers indicating carcinogenesis. CA-125 levels did not seem to undermine the high classification accuracies. This minimally invasive test may provide an alternative diagnostic and screening tool for ovarian cancer that is superior to other established blood-based biomarkers. [Abstract copyright: Copyright © 2018 Elsevier B.V. All rights reserved.]
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- 2018
19. Spectral classification for diagnosis involving numerous pathologies in a complex clinical setting: A neuro-oncology example
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Bury, Danielle Elizabeth, Medeiros-De-morais, Camilo De lelis, Paraskevaidi, Maria, Ashton, Katherine M., Dawson, Timothy, Martin, Francis L, Bury, Danielle Elizabeth, Medeiros-De-morais, Camilo De lelis, Paraskevaidi, Maria, Ashton, Katherine M., Dawson, Timothy, and Martin, Francis L
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Much effort is currently being placed into developing new blood tests for cancer diagnosis in the hope of moving cancer diagnosis earlier and by less invasive means than current techniques, e.g., biopsy. Current methods are expected to diagnose and begin treatment of cancer within 62 days of patient presentation, though due to high volume and pressures within the NHS in the UK any technique that can reduce time to diagnosis would allow reduction in the time to treat for patients. The use of vibrational spectroscopy, notably infrared (IR) spectroscopy, has been under investigation for many years with varying success. This technique holds promise as is would combine a generally well accepted test (a blood test) with analysis that is reagent free and cheap to run. It has been demonstrated that, when asked simple clinical questions (i.e., cancer vs. no cancer), results from spectroscopic studies are promising. However, in order to become a clinically useful tool, it is important that the test differentiates a variety of cancer types from healthy patients. This study has analysed plasma samples with attenuated total reflection Fourier-transform IR spectroscopy (ATR-FTIR), to establish if the technique is able to distinguish normal from primary or metastatic brain tumours. We have shown that when asked specific questions, i.e., high-grade glioma vs. low-grade glioma, the results show a significantly high accuracy (100%). Crucially, when combined with meningiomas and metastatic lesions, the accuracy remains high (88-100%) with only minimal overlap between the two metastatic adenocarcinoma groups. Therefore in a clinical setting, this novel technique demonstrates potential benefit when used in conjuction with existing diagnostic methods. [Abstract copyright: Copyright © 2018 Elsevier B.V. All rights reserved.]
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- 2018
20. Increased exposure to pesticides and colon cancer: Early evidence in Brazil
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Martin, Francis L, Martinez, Edson Z., Stopper, Helga, Garcia, Sergio Britto, Uyemura, Sergio Akira, Kannen, Vinicius, Martin, Francis L, Martinez, Edson Z., Stopper, Helga, Garcia, Sergio Britto, Uyemura, Sergio Akira, and Kannen, Vinicius
- Abstract
Environmental factors may increase colon cancer (CC) risk. It has been suggested that pesticides could play a significant role in the etiology of this malignancy. As agriculture is one of the mainstays of the Brazilian economy, this country has been the largest pesticides consumer worldwide. The CC burden is also increasing in Brazil. Herein, we examined data from the Brazilian Federal Government to determine whether CC mortality and pesticide consumption may be associated. Database of the Ministry of Health provided CC mortality data in Brazil, while pesticides use was accessed at the website of Brazilian Institute of Environment and Renewable Natural Resources. The CC mortality in the Brazilian states was calculated as standard mortality rates (SMR). All Bayesian analysis was performed using a Markov chain Monte Carlo method in WinBUGS software. We observed that colon cancer mortality has exhibited a steady increase for more than a decade, which correlated with the amount of sold pesticides in the country. Both observations are concentrated in the Southern and the Southeast regions of Brazil. Although ecological studies like ours have methodological limitations, the current dataset suggests the possibility that pesticide exposure may be a risk factor for colon cancer. It warrants further investigation.
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- 2018
21. 4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells
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Martin, Francis L and Martin, Francis L
- Abstract
The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the “nursemaid cells” for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100 mg/kg body weight/2 days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10 µM Compound C or AMPKα1 siRNA pre-treatment effectively attenuated autophagy and reversed AMPK-mTOR-p70S6K/4EBP1 signaling in NP-treated SCs. Co-treatment with 1 mM AICAR remarkably strengthened NP-induced autophagy and mTOR inhibition in SCs. Together, these data suggest that NP stimulates Sertoli cell autophagy and inhibits mTOR-p70S6K/4EBP1 activity through AMPK activation, which is the potential mechanism responsible for the regulation of testis function and differentiation following NP exposure.
- Published
- 2017
22. Are new technologies translatable to point-of-care testing?
- Author
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Bury, Danielle Elizabeth, Martin-Hirsch, Pierre L, Martin, Francis L, Dawson, Timothy P, Bury, Danielle Elizabeth, Martin-Hirsch, Pierre L, Martin, Francis L, and Dawson, Timothy P
- Published
- 2017
23. Detecting nutrient deficiency in plant systems using synchrotron Fourier-transform infrared microspectroscopy
- Author
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Butler, Holly J., Adams, Steve, McAinsh, Martin R., Martin, Francis L, Butler, Holly J., Adams, Steve, McAinsh, Martin R., and Martin, Francis L
- Abstract
By 2050, it is estimated that the global population will have surpassed 9 billion people, presenting a significant challenge with regards to food security. In order to provide sufficient quantities of nutritious food in the future, it is necessary to improve agricultural productivity by up to 70%. Nutrient deficiencies are one particular threat to food security that can have a negative impact on crop yield and quality. Currently the standard agricultural approach to prevention is to supply an excess macronutrient fertiliser, such as nitrate or phosphate, during crop production. However, the efficiency of this approach is poor as deficiencies of specific nutrients, such as Ca, are not prevented in this circumstance, and fertiliser use is associated with a host of adverse environmental impacts. Herein, we describe a novel method to detect Ca deficiency using synchrotron radiation-based Fourier-transform infrared (FTIR) microspectroscopy in live and fixed tissue of the model plant Commelina communis, as a precursor to targeted nutrient remediation in the field.
- Published
- 2017
24. Spatial and temporal age-related spectral alterations in benign human breast tissue
- Author
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Theophilou, Georgios, Fogarty, Simon, Trevisan, Julio, Strong, Becky, Heys, Kelly, Patel, Imran, Stringfellow, Helen F., Martin-Hirsch, Pierre Leonard, Martin, Francis L, Theophilou, Georgios, Fogarty, Simon, Trevisan, Julio, Strong, Becky, Heys, Kelly, Patel, Imran, Stringfellow, Helen F., Martin-Hirsch, Pierre Leonard, and Martin, Francis L
- Abstract
Epidemiological evidence suggests that cancers attributable to exogenous carcinogenic agents may appear decades after initiating exposures. Environmental factors including lifestyle and/or diet have been implicated in the aetiology of breast cancer. Breast tissue undergoes continuous molecular and morphological changes from the time of thelarche to menopause and thereafter. These alterations are both cyclical and longitudinal, and can be influenced by several environmental factors including exposure to oestrogens. Research into the latent period leading to breast carcinogenesis has been mostly limited to when hyperplastic lesions are present. Investigations to identify a biomarker of commitment to disease in normal breast tissue are hindered by the molecular and histological diversity of disease-free breast tissue. Benign tissue from reduction mammoplasties provides an opportunity to study biochemical differences between women of similar ages as well as alterations with advancing age. Herein, synchrotron radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy was used to examine the terminal ductal lobular epithelium (TDLU) and, intra- and inter-lobular epithelium to identify spatial and temporal changes within these areas. Principal component analysis (PCA) followed by linear discriminant analysis of mid-infrared spectra revealed unambiguous inter-individual as well as age-related differences in each histological compartment interrogated. Moreover, exploratory PCA of luminal and myoepithelial cells within the TDLU indicated the presence of specific cells, potentially stem cells. Understanding alterations within benign tissue may assist in the identification of alterations in latent pre-clinical stages of breast cancer.
- Published
- 2016
25. ATR-FTIR spectroscopy reveals polycyclic aromatic hydrocarbon contamination despite relatively pristine site characteristics:results of a field study in the Niger Delta
- Author
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Obinaju, Blessing, Martin, Francis L, Obinaju, Blessing, and Martin, Francis L
- Abstract
Fourier-transform infrared (FTIR) spectroscopy is an emerging technique to detect biochemical alterations in biological tissues, particularly changes due to sub-lethal exposures to environmental contaminants. We have previously shown the potential of attenuated total reflection FTIR (ATR-FTIR) spectroscopy to detect real-time exposure to contaminants in sentinel organisms as well as the potential to relate spectral alterations to the presence of specific environmental agents. In this study based in the Niger Delta (Nigeria), changes occurring in fish tissues as a result of polycyclic aromatic hydrocarbon (PAH) exposure at contaminated sites are compared to the infrared (IR) spectra of the tissues obtained from a relatively pristine site. Multivariate analysis revealed that PAH contamination could be occurring at the pristine site, based on the IR spectra and significant (P < 0.0001) differences between sites. The study provides evidence of the IR spectroscopy techniques' sensitivity and supports their potential application in environmental biomonitoring.
- Published
- 2016
26. Overcoming barriers to non-animal risk assessments for anti-androgenic effects in humans
- Author
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Dent, M., Carmichael, P., Vantangoli, M., Boekelheide, K., Martin, Francis L, Dent, M., Carmichael, P., Vantangoli, M., Boekelheide, K., and Martin, Francis L
- Abstract
Toxicology testing is undergoing a transformation from a system based on high-dose studies in animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. This is a challenge for anti-androgenic effects in humans, since some parts of the hypothalamus-pituitary-testicular axis are not well represented by accepted in vitro methods. These include key events relating to gonadotropin releasing hormone (GnRH) signalling which could be affected at the level of the hypothalamus and pituitary. In vitro tools are needed to characterize either specific effects (such as GnRH receptor antagonism) or non-specific effects (such as general toxicity causing a reduction in gonadotropin release) before an integrated model of the HPT axis can be described. We have been evaluating how this could be achieved using human non-pituitary cells that express GnRH receptors and synthesize gonadotropins. Furthermore, tools to characterize a tipping point between endocrine activity and adversity need to be developed to allow an assessment that is more representative of the underlying biological response to endocrine active chemicals. To this end we have been developing and characterizing human derived scaffold-free prostate microtissues to provide morphological and molecular readouts to identify exposures that lead to adverse responses. Our ambition is to use these tools in an exposure-led safety assessment to enable robust safety decision making for endocrine active chemicals without use of animals ( Dent et al., 2015).
- Published
- 2016
27. Effects of 4-Nonylphenol on spermatogenesis and induction of testicular apoptosis through oxidative stress-related pathways
- Author
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Duan, Peng, Hu, Chunhui, Butler, Holly, Chen, Wei, Huang, Wenting, Tang, Sha, Zhou, Wei, Yuan, Meng, Shi, Yuqin, Martin, Francis L, Yang, Kedi, Duan, Peng, Hu, Chunhui, Butler, Holly, Chen, Wei, Huang, Wenting, Tang, Sha, Zhou, Wei, Yuan, Meng, Shi, Yuqin, Martin, Francis L, and Yang, Kedi
- Abstract
This study tested the hypothesis that prepubertal exposure to 4-Nonylphenol (NP) affects reproductive function in male rats. Twenty-four rats at five-weeks-old were randomly divided into four groups and treated with NP at varying concentrations (0, 5, 20, and 60 mg/kg/2d) for thirty days by intra-peritoneal injection. 60 mg/kg NP induced spermatogenic degeneration and pronounced deficits in epididymal sperm count, motility and function, whereas potentially stimulatory effects were observed at 5 NP mg/kg. Moreover, 60 mg/kg NP resulted in a significant reduction in fructose, FSH and LH; induced apoptosis related to oxidative stress; inhibited mRNA and protein levels of Bcl-2 and PCNA; as well as the additional up-regulation of p53, Bax, Apaf-1, cytochrome c, cleaved-caspase-3, Fas and FasL expression. Our data suggest potentially hormetic effects of NP on spermatogenic function. High-dose NP impairs testicular development and function by reducing cell proliferation and inducing apoptosis involving oxidative stress-related p53-Bcl-2/Bax and ?Fas/FasL pathways.
- Published
- 2016
28. Biospectroscopy reveals the effect of varying water quality on tadpole tissues of the common frog (Rana temporaria)
- Author
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Strong, Becky, Halsall, Crispin James, Ferenčík, Martin, Jones, Kevin Christopher, Shore, Richard Francis, Martin, Francis L, Strong, Becky, Halsall, Crispin James, Ferenčík, Martin, Jones, Kevin Christopher, Shore, Richard Francis, and Martin, Francis L
- Abstract
Amphibians are undergoing large population declines in many regions around the world. As environmental pollution from both agricultural and urban sources has been implicated in such declines, there is a need for a biomonitoring approach to study potential impacts on this vulnerable class of organism. This study assessed the use of infrared (IR) spectroscopy as a tool to detect changes in several tissues (liver, muscle, kidney, heart and skin) of late-stage common frog (Rana temporaria) tadpoles collected from ponds with differing water quality. Small differences in spectral signatures were revealed between a rural agricultural pond and an urban pond receiving wastewater and landfill run-off; these were limited to the liver and heart, although large differences in body size were apparent, surprisingly with tadpoles from the urban site larger than those from the rural site. Large differences in liver spectra were found between tadpoles from the pesticide and nutrient impacted pond compared to the rural agricultural pond, particularly in regions associated with lipids. Liver mass and hepatosomatic indices were found to be significantly increased in tadpoles from the site impacted by pesticides and trace organic chemicals, suggestive of exposure to environmental contamination. Significant alterations were also found in muscle tissue between tadpoles from these two ponds in regions associated with glycogen, potentially indicative of a stress response. This study highlights the use of IR spectroscopy, a low-cost, rapid and reagent-free technique in the biomonitoring of a class of organisms susceptible to environmental degradation.
- Published
- 2016
29. Infrared spectroscopy detects changes in an amphibian cell line induced by fungicides:comparison of single and mixture effects
- Author
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Strong, Becky, Halsall, Crispin James, Jones, Kevin Christopher, Shore, Richard Francis, Martin, Francis L, Strong, Becky, Halsall, Crispin James, Jones, Kevin Christopher, Shore, Richard Francis, and Martin, Francis L
- Abstract
Amphibians are regarded as sensitive sentinels of environmental pollution due to their permeable skin and complex life cycle, which usually involves reproduction and development in the aquatic environment. Fungicides are widely applied agrochemicals and have been associated with developmental defects in amphibians; thus, it is important to determine chronic effects of environmentally-relevant concentrations of such contaminants in target cells. Infrared (IR) spectroscopy has been employed to signature the biological effects of environmental contaminants through extracting key features in IR spectra with chemometric methods. Herein, the Xenopus laevis (A6) cell line was exposed to low concentrations of carbendazim (a benzimidazole fungicide) or flusilazole (a triazole fungicide) either singly or as a binary mixture. Cells were then examined using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy coupled with multivariate analysis. Results indicate significant changes in the IR spectra of cells induced by both agents at all concentrations following single exposures, primarily in regions associated with protein and phospholipids. Distinct differences were apparent in the IR spectra of cells exposed to carbendazim and those exposed to flusilazole, suggesting different mechanisms of action. Exposure to binary mixtures of carbendazim and flusilazole also induced significant spectral alterations, again in regions associated with phospholipids and proteins, but also in regions associated with DNA and carbohydrates. Overall these findings demonstrate that IR spectroscopy is a sensitive technique for examining the effects of environmentally-relevant levels of fungicides at the cellular level. The combination of IR spectroscopy with the A6 cell line could serve as a useful model to identify agents that might threaten amphibian health in a rapid and high throughput manner.
- Published
- 2016
30. Infrared spectroscopy detects changes in an amphibian cell line induced by fungicides: comparison of single and mixture effects
- Author
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Strong, Rebecca J., Halsall, Crispin J., Jones, Kevin C., Shore, Richard F., Martin, Francis L., Strong, Rebecca J., Halsall, Crispin J., Jones, Kevin C., Shore, Richard F., and Martin, Francis L.
- Abstract
Amphibians are regarded as sensitive sentinels of environmental pollution due to their permeable skin and complex life cycle, which usually involves reproduction and development in the aquatic environment. Fungicides are widely applied agrochemicals and have been associated with developmental defects in amphibians; thus, it is important to determine chronic effects of environmentally-relevant concentrations of such contaminants in target cells. Infrared (IR) spectroscopy has been employed to signature the biological effects of environmental contaminants through extracting key features in IR spectra with chemometric methods. Herein, the Xenopus laevis (A6) cell line was exposed to low concentrations of carbendazim (a benzimidazole fungicide) or flusilazole (a triazole fungicide) either singly or as a binary mixture. Cells were then examined using attenuated total reflection Fouriertransform IR (ATR-FTIR) spectroscopy coupled with multivariate analysis. Results indicate significant changes in the IR spectra of cells induced by both agents at all concentrations following single exposures, primarily in regions associated with protein and phospholipids. Distinct differences were apparent in the IR spectra of cells exposed to carbendazim and those exposed to flusilazole, suggesting different mechanisms of action. Exposure to binary mixtures of carbendazim and flusilazole also induced significant spectral alterations, again in regions associated with phospholipids and proteins, but also in regions associated with DNA and carbohydrates. Overall these findings demonstrate that IR spectroscopy is a sensitive technique for examining the effects of environmentally-relevant levels of fungicides at the cellular level. The combination of IR spectroscopy with the A6 cell line could serve as a useful model to identify agents that might threaten amphibian health in a rapid and high throughput manner.
- Published
- 2016
31. Biospectroscopy reveals the effect of varying water quality on tadpole tissues of the common frog (Rana temporaria)
- Author
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Strong, Rebecca J., Halsall, Crispin J., Ferenčík, Martin, Jones, Kevin C., Shore, Richard F., Martin, Francis L., Strong, Rebecca J., Halsall, Crispin J., Ferenčík, Martin, Jones, Kevin C., Shore, Richard F., and Martin, Francis L.
- Abstract
Amphibians are undergoing large population declines in many regions around the world. As environmental pollution from both agricultural and urban sources has been implicated in such declines, there is a need for a biomonitoring approach to study potential impacts on this vulnerable class of organism. This study assessed the use of infrared (IR) spectroscopy as a tool to detect changes in several tissues (liver, muscle, kidney, heart and skin) of late-stage common frog (Rana temporaria) tadpoles collected from ponds with differing water quality. Small differences in spectral signatures were revealed between a rural agricultural pond and an urban pond receiving wastewater and landfill run-off; these were limited to the liver and heart, although large differences in body size were apparent, surprisingly with tadpoles from the urban site larger than those from the rural site. Large differences in liver spectra were found between tadpoles from the pesticide and nutrient impacted pond compared to the rural agricultural pond, particularly in regions associated with lipids. Liver mass and hepatosomatic indices were found to be significantly increased in tadpoles from the site impacted by pesticides and trace organic chemicals, suggestive of exposure to environmental contamination. Significant alterations were also found in muscle tissue between tadpoles from these two ponds in regions associated with glycogen, potentially indicative of a stress response. This study highlights the use of IR spectroscopy, a low-cost, rapid and reagent-free technique in the biomonitoring of a class of organisms susceptible to environmental degradation.
- Published
- 2016
32. Towards a non-animal risk assessment for anti-androgenic effects in humans
- Author
-
Dent, Matthew P., Carmichael, Paul L., Jones, Kevin C., Martin, Francis L, Dent, Matthew P., Carmichael, Paul L., Jones, Kevin C., and Martin, Francis L
- Abstract
Toxicology testing is undergoing a transformation from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. We review the tools and approaches that could be used to develop a non-animal safety assessment for anti-androgenic effects in humans, with a focus on the molecular initiating events (MIEs) that human disorders indicate critical for normal functioning of the hypothalamus-pituitary-testicular (HPT) axis. In vitro test systems exist which can be used to characterize the effects of test chemicals on some MIEs such as androgen receptor antagonism, inhibition of steroidogenic enzymes or 5\ensuremathα-reductase inhibition. When used alongside information describing the pharmacokinetics of a specific chemical exposure, these could be used to inform a pathways-based safety assessment. However, some parts of the HPT axis such as events occurring in the hypothalamus or pituitary are not well represented by accepted in vitro methods. In vitro tools to characterize perturbations in these events need to be developed before a fully integrated model of the HPT axis can be described. Knowledge gaps also exist which prevent us from using in vitro data to predict the type and severity of in vivo effect(s) that could arise from a given level of in vitro anti-androgenic activity. This means that more work is needed to reliably link an MIE with an adverse outcome. However, especially for chemicals with low anti-androgenic activity, human exposure data can be used to put in vitro mode of action data into context for risk-based safety decision-making.
- Published
- 2015
33. Interrogating chemical variation via layer-by-layer SERS during biofouling and cleaning of nanofiltration membranes with further investigations into cleaning efficiency
- Author
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Cui, Li, Chen, Pengyu, Zhang, Bifeng, Zhang, Dayi, Li, Junyi, Martin, Francis L, Zhang, Kaisong, Cui, Li, Chen, Pengyu, Zhang, Bifeng, Zhang, Dayi, Li, Junyi, Martin, Francis L, and Zhang, Kaisong
- Abstract
Periodic chemical cleaning is an essential step to maintain nanofiltration (NF) membrane performance and mitigate biofouling, a major impediment in high-quality water reclamation from wastewater effluent. To target the important issue of how to clean and control biofouling more efficiently, this study developed surface-enhanced Raman spectroscopy (SERS) as a layer-by-layer tool to interrogate the chemical variations during both biofouling and cleaning processes. The fact that SERS only reveals information on the surface composition of biofouling directly exposed to cleaning reagents makes it ideal for evaluating cleaning processes and efficiency. SERS features were highly distinct and consistent with different biofouling stages (bacterial adhesion, rapid growth, mature and aged biofilm). Cleaning was performed on two levels of biofouling after 18 h (rapid growth of biofilm) and 48 h (aged biofilm) development. An opposing profile of SERS bands between biofouling and cleaning was observed and this suggests a layer-by-layer cleaning mode. In addition, further dynamic biochemical and infrastructural changes were demonstrated to occur in the more severe 48-h biofouling, resulting in the easier removal of sessile cells from the NF membrane. Biofouling substance-dependent cleaning efficiency was also evaluated using the surfactant sodium dodecyl sulfate (SDS). SDS appeared more efficient in cleaning lipid than polysaccharide and DNA. Protein and DNA were the predominant residual substances (irreversible fouling) on NF membrane leading to permanent flux loss. The chemical information revealed by layer-by-layer SERS will lend new insights into the optimization of cleaning reagents and protocols for practical membrane processes.
- Published
- 2015
34. Association of environmental benzoapyrene exposure and DNA methylation alterations in hepatocellular carcinoma: a Chinese case-control study
- Author
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Tian, Meiping, Zhao, Benhua, Zhang, Jie, Martin, Francis L, Huang, Qingyu, Liu, Liangpo, Shen, Heqing, Tian, Meiping, Zhao, Benhua, Zhang, Jie, Martin, Francis L, Huang, Qingyu, Liu, Liangpo, and Shen, Heqing
- Abstract
Epidemiological studies implicate environmental risk factors and epigenetic alterations in the multistage process of hepatocellular carcinoma (HCC) development. However, associations between environmental factors and DNA methylation of tumour suppressor genes (TSGs) in HCC development remain ambiguous. Understanding how possible interactions influence risk may provide insights into the complexity of hepato-carcinogenesis. For this study, blood samples were collected from HCC patients (n = 90) and healthy volunteers (n = 99) from Xiamen (China) and data for selected environmental risk factors e.g., benzoa]pyrene (BaP), hepatitis B or C virus (HBV or HCV) infection, smoking and alcohol consumption were recorded; factors identified as significantly higher (P {\ensuremath{<}} 0.05) amongst case subjects compared to controls were identified. In order to assess associations for epigenetic alterations and HCC risk factors, serum DNA methylation of TSGs was quantified using high-resolution melting (HRM) analysis. Our results clearly indicate elevated methylation patterns for detoxification gene glutathione-S-transferase Pi (GSTP) promoter regions in cases compared to control subjects. Additionally, GSTP promoter hypermethylation and BaP diol epoxide-albumin (BPDE-Alb) were positively correlated with HCC incidence. Our epidemiological and in vitro cell model studies indicated that GSTP promoter DNA methylation regulates this gene's expression. Moreover, GSTP also plays an important role in BaP detoxification and potential protective role against BaP-induced liver cell toxicity and hepato-carcinogenesis.
- Published
- 2015
35. Linking biochemical perturbations in tissues of the African catfish to the presence of polycyclic aromatic hydrocarbons in Ovia River, Niger Delta region
- Author
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Obinaju, Blessing E., Graf, Carola, Halsall, Crispin, Martin, Francis L, Obinaju, Blessing E., Graf, Carola, Halsall, Crispin, and Martin, Francis L
- Abstract
Petroleum hydrocarbons including polycyclic aromatic hydrocarbons (PAHs) are a pollution issue in the Niger Delta region due to oil industry activities. PAHs were measured in the water column of the Ovia River with concentrations ranging from 0.1 to 1055.6 ng L-1. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy detected alterations in tissues of the African catfish (Heter-bronchus bidorsalis) from the region showed varying degrees of statistically significant (P <0.0001, P <0.001, P <0.05) changes to absorption band areas and shifts in centroid positions of peaks. Alteration patterns were similar to those induced by benzoapyrene in MCF-7 cells. These findings have potential health implications for resident local communities as H. bidorsalis constitutes a key nutritional source. The study provides supporting evidence for the sensitivity of infrared spectroscopy in environmental studies and supports their potential application in biomonitoring. (C) 2015 Elsevier Ltd. All rights reserved.
- Published
- 2015
36. Novel sensor technologies towards environmental health monitoring in urban environments:a case study in the Niger Delta (Nigeria)
- Author
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Obinaju, Blessing, Alaoma, Alozie, Martin, Francis L, Obinaju, Blessing, Alaoma, Alozie, and Martin, Francis L
- Abstract
The Niger Delta (Nigeria) is an exemplar of a legacy of environmental pollution. Limited knowledge on spatial and temporal pollutant distributions in the region highlights the need for biomonitoring approaches to study impacts on sentinel organisms. This study evaluated whether infrared (IR) spectroscopy and multivariate analysis could detect alterations in biomolecules in samples in differing exposure scenarios, i.e., spatial and temporal using African catfish (Heterobranchus bidorsalis) or water spinach (Ipomea aquatica). Significant spectral differences between tissues isolated from African catfish based on site or season were observed; in a region where fish appeared not to be present, water spinach was used as a surrogate sentinel organism. Using one-way ANOVA, the spectral categories were significant (P < 0.0001). The applicability of IR spectroscopy to detect subtle changes in target biological molecules within sentinel organisms along with its low-cost yet high-throughput potential suggests that biospectroscopy permits real-time evaluation of environmental exposure effects.
- Published
- 2014
37. Bimodal responses of cells to trace elements:insights into their mechanism of action using a biospectroscopy approach
- Author
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Llabjani, Valon, Llabjani, Valmira Hoti, Pouran, Hamid Mohammad, Martin, Francis L, Zhang, Hao, Llabjani, Valon, Llabjani, Valmira Hoti, Pouran, Hamid Mohammad, Martin, Francis L, and Zhang, Hao
- Abstract
Understanding how organisms respond to trace elements is important because some are essential for normal bodily homeostasis, but can additionally be toxic at high concentrations. The inflection point for many of these elements is unknown and requires sensitive techniques capable of detecting subtle cellular changes as well as cytotoxic alterations. In this study, we treated human cells with arsenic (As), copper or selenium (Se) in a dose?response manner and used attenuated total reflection Fourier-transform infrared (ATR-FTIR) microspectroscopy combined with computational analysis to examine cellular alterations. Cell cultures were treated with Asv, Cu2+ or Seiv at concentrations ranging from 0.001 mg L?1 to 1000 mg L?1 and their effects were spectrochemically determined. Results show that Asv and Cu2+ induce bimodal dose?response effects on cells; this is in line with hormesis-driven responses. Lipids and proteins seem to be the main cell targets for all the elements tested; however, each compound produced a unique fingerprint of effect. Spectral biomarkers indicate that all test agents generate reactive oxygen species (ROS), which could either stimulate repair mechanisms or induce damage in cells.
- Published
- 2014
38. Interactions of multiwalled carbon nanotubes with algal cells:quantification of association, visualization of uptake, and measurement of alterations in the composition of cells
- Author
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Rhiem, Stefan, Riding, Matthew J., Baumgartner, Werner, Martin, Francis L, Semple, Kirk T., Jones, Kevin C., Schäffer, Andreas, Maes, Hanna M., Rhiem, Stefan, Riding, Matthew J., Baumgartner, Werner, Martin, Francis L, Semple, Kirk T., Jones, Kevin C., Schäffer, Andreas, and Maes, Hanna M.
- Abstract
Carbon nanotubes (CNTs) are considered promising materials in nanotechnology. We quantified CNT accumulation by the alga Desmodesmus subspicatus. Cells were exposed to radiolabeled CNTs ((14)C-CNTs; 1 mg/L) to determine uptake and association, as well as elimination and dissociation in clear media. Attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) was used to detect effects of CNTs on algae. CNT-cell interactions were visualized by electron microscopy and related to alterations in their cell composition. A concentration factor of 5000 L/kg dry weight was calculated. Most of the material agglomerated around the cells, but single tubes were detected in the cytoplasm. Computational analyses of the ATR-FTIR data showed that CNT treated algae differed from controls at all sampling times. CNT exposure changed the biochemical composition of cells. The fact that CNTs are bioavailable for algae and that they influence the cell composition is important with regard to environmental risk assessment of this nanomaterial.
- Published
- 2014
39. Chemical measures of bioavailability/bioaccessibility of PAHs in soil:fundamentals to application
- Author
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Riding, Matthew J., Doick, Kieron J., Martin, Francis L, Jones, Kevin C., Semple, Kirk T., Riding, Matthew J., Doick, Kieron J., Martin, Francis L, Jones, Kevin C., and Semple, Kirk T.
- Abstract
Risk assessment and remediation of contaminated land is inherently dependent on the contaminants present and their availability for interaction with soil biota. An ever-growing body of evidence suggests that current regulatory procedures over-estimate the 'true' fraction available to biota. Thus, a procedure that predicts the 'bioavailable fraction' would be useful for predicting 'actual' exposure limits and provide a more relevant basis for risk assessment. The aim of this paper is to address several important questions: "How should bioavailability be defined?" "What factors affect bioavailability measurement?" "To what extent have existing protocols measured bioavailability?" "What is actually measured by chemical techniques purported to determine bioavailability?" We offer two definitions (namely 'bioavailability' and 'bioaccessibility') and review commonly employed chemical extraction techniques to measure putative bioavailability. Relative advantages and disadvantages of the techniques are highlighted to elucidate underlying factors for the wide range of conclusions observed in the literature. Although the concept of bioavailability is implicit to contaminated land risk assessment and remediation, explicit reference to and use of adjustment factors is rare amongst regulatory bodies and remediators. Use of chemical determinants for bioavailability, applicable within current legislation and due consideration to inherent variability, are proposed and barriers to their implementation discussed.
- Published
- 2013
40. Concentration-dependent effects of carbon nanoparticles in gram-negative bacteria determined by infrared spectroscopy with multivariate analysis
- Author
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Riding, Matthew J., Martin, Francis L, Trevisan, Julio, Llabjani, Valon, Patel, Imran I., Jones, Kevin C., Semple, Kirk T., Riding, Matthew J., Martin, Francis L, Trevisan, Julio, Llabjani, Valon, Patel, Imran I., Jones, Kevin C., and Semple, Kirk T.
- Abstract
With increasing production of carbon nanoparticles (CNPs), environmental release of these entities becomes an ever-greater inevitability. However, many questions remain regarding their impact on soil microorganisms. This study examined the effects of long or short multiwalled carbon nanotubes (MWCNTs), C60 fullerene and fullerene soot in Gram-negative bacteria. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy was applied to derive signature spectral fingerprints of effects. A concentration-dependent response in spectral alterations was observed for each nanoparticle type. Long or short MWCNTs and fullerene soot gave rise to similar alterations to lipids, Amide II and DNA. The extent of alteration varies with nanoparticle size, with smaller short MWCNTs resulting in greater toxicity than long MWCNTs. Fullerene soot was the least toxic. C60 results in the most distinct and largest overall alterations, notably in extensive protein alteration. This work demonstrates a novel approach for assaying and discriminating the effects of CNPs in target systems. (C) 2011 Elsevier Ltd. All rights reserved.
- Published
- 2012
41. Mechanistic insights into nanotoxicity determined by synchrotron radiation-based Fourier-transform infrared imaging and multivariate analysis
- Author
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Riding, Matthew J., Trevisan, Júlio, Hirschmugl, Carol J., Jones, Kevin C., Semple, Kirk T., Martin, Francis L, Riding, Matthew J., Trevisan, Júlio, Hirschmugl, Carol J., Jones, Kevin C., Semple, Kirk T., and Martin, Francis L
- Abstract
Our ability to identify the mechanisms by which carbon-based nanomaterials (CBNs) exert toxicity in cells is constrained by the lack of standardized methodologies to assay endpoint effects. Herein we describe a method of mechanistically identifying the effects of various CBN types in both prokaryotic and eukaryotic cells using multi-beam synchrotron radiation-based Fourier-transform infrared imaging (SR-FTIRI) at diffraction-limited resolution. This technique overcomes many of the inherent difficulties of assaying nanotoxicity and demonstrates exceptional sensitivity in identifying the effects of CBNs in cells at environmentally-relevant concentrations. We identify key mechanisms of nanotoxicity as the alteration of Amide and lipid biomolecules, but propose more specific bioactivity of CBNs occurs as a result of specific interactions between CBN structural conformation and cellular characteristics.
- Published
- 2012
42. Identification of benzoapyrene-induced cell cycle-associated alterations in MCF-7 cells using infrared spectroscopy with computational analysis
- Author
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Pang, Weiyi, Li, Junyi, Ahmadzai, Abdullah A, Heppenstall, Lara D, Llabjani, Valon, Trevisan, Júlio, Qiu, Xiaoqiang, Martin, Francis L, Pang, Weiyi, Li, Junyi, Ahmadzai, Abdullah A, Heppenstall, Lara D, Llabjani, Valon, Trevisan, Júlio, Qiu, Xiaoqiang, and Martin, Francis L
- Abstract
Chemical contaminants, such as benzoapyrene (BaP), may modulate transcriptional responses in cells via the activation of aryl hydrocarbon receptor (AhR) or through responses to DNA damage following adduct formation. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy can be employed in a non-destructive fashion to interrogate the biochemical signature of cells via generation of infrared (IR) spectra. By applying to generated spectral datasets subsequent computational approaches such as principal component analysis plus linear discriminant analysis (PCA-LDA), derived data reduction is achieved to facilitate the visualization of wavenumber-related alterations in target cells. Discriminating spectral variables might be associated with lipid or glycogen content, conformational protein changes and phosphorylation, and structural alterations in DNA/RNA. Using this approach, we investigated the dose-related effects of BaP in MCF-7 cells concentrated in S- or G{$_0$}/G{$_1$}-phase. Our findings identified that in PCA-LDA scores plots a clear segregation of IR spectra was evident, with the major spectral alterations associated with DNA/RNA, secondary protein structure and lipid. Dose-related effects were observed and even with exposures as low as 10{$^-$}{$^9$} M BaP, significant (P {$\leq$} 0.001) separation of BaP-treated vs. vehicle control cells was noted. ATR-FTIR spectroscopy with computational analysis is a novel approach to identify the effects of environmental contaminants in target cells.
- Published
- 2012
43. Cytochrome P1B1 gene (CYP1B1) polymorphisms and ovarian cancer risk:a meta-analysis
- Author
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Gajjar, Ketan, Owens, Gemma, Sperrin, Matthew, Martin-Hirsch, Pierre L, Martin, Francis L, Gajjar, Ketan, Owens, Gemma, Sperrin, Matthew, Martin-Hirsch, Pierre L, and Martin, Francis L
- Abstract
CYP1B1 is a key P450 enzyme involved in the metabolism of exogenous and endogenous substrates and plays a key role in hormone-induced carcinogenesis. Risk factors for ovarian cancer are related to hormonal exposure and reproduction, and polymorphisms within genes involved in metabolism of oestrogen and certain xenobiotics may influence the risk of developing ovarian cancer. Current meta-analysis evaluated four CYP1B1 polymorphisms (Leu432Val, Arg48Gly, Ala119Ser and Asn453Ser) for their association with ovarian cancer risk. A search of MEDLINE bibliographic database for the period up to April 2012 identified five studies. With regards to Leu432Val polymorphism, all of the five studies were eligible (1199 cases and 2596 controls) for analysis, while for Arg48Gly (799 cases and 1169 controls), Ala119Ser (799 cases and 1172 controls) and Asn453Ser (361cases and 1577 controls) only two studies were eligible for analysis. Fixed-effect models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (95% CI) and chi-square based Q-test was used to test for heterogeneity. The pooled OR (95% CI) for CYP1B1_Leu432Val polymorphism were 1.1 (0.84-1.31) for heterozygous subjects and 0.82 (0.57-1.17) for homozygous Val subjects. In a recessive model, homozygous carriers of Leu432Val showed a weak trend towards reduced risk as compared to 'wild type' and heterozygous carriers (OR 0.8, 95% CI; 0.66-0.99); however, this association was of limited significance. Regarding Arg48Gly, the pooled OR (95% CI) were 1.06 (0.89-1.27) for heterozygous and 0.98 (1.72-1.33) for homozygous Gly subjects. With respect to Ala119Ser and Asn453Ser, the pooled OR were 1.06 (0.87-1.29) and 1.24 (0.94-1.63) for heterozygous and 1.1 (0.8-1.52) and 1.09 (0.5-2.34) for homozygous respectively. In conclusion, this meta-analysis suggests that CYP1B1 polymorphisms are not associated with ovarian cancer risk. Studies evaluating CYP1B1_Leu432Val polymorphism are required to further elucidate t
- Published
- 2012
44. Alterations in the infrared spectral signature of avian feathers reflect potential chemical exposure:a pilot study comparing two sites in Pakistan
- Author
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Llabjani, Valon, Malik, Riffat N., Trevisan, Julio, Llabjani, Valmira Hoti, Ukpebor, Justina, Shinwari, Zabta K., Moeckel, Claudia, Jones, Kevin C., Shore, Richard F., Martin, Francis L, Llabjani, Valon, Malik, Riffat N., Trevisan, Julio, Llabjani, Valmira Hoti, Ukpebor, Justina, Shinwari, Zabta K., Moeckel, Claudia, Jones, Kevin C., Shore, Richard F., and Martin, Francis L
- Abstract
Chemical contamination of ecosystems is a global issue with evidence that pollutants impact on living organisms in a harmful fashion. Developing sensor approaches that would allow the derivation of biomarkers or signatures of effect in target sentinel organisms and monitor environmental chemical contamination in a high throughput manner is of utmost importance. As biomolecules absorb infrared (IR), signature vibrational spectra related to structure and function can be derived. In light of this, we tested the notion that IR spectra of bird feathers might reflect environmental chemical contaminant exposure patterns. Feathers were collected from monospecific heronries of cattle egret based in two independent locations (Trimu vs. Mailsi) in the Punjab province of Pakistan; these sites were found to differ in their chemical contamination patterns. Feather samples were chemically analyzed for polychlorinated biphenyls, polybrominated diphenyl ethers, organochlorines and heavy metals. Attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy was employed to derive a spectral signature of individual feathers. Resultant IR spectra were then subjected to canonical correspondence analysis (CAA) to determine whether feather spectral signatures correlate to chemical exposure. Additionally, we explored if principal component analysis (PCA) and linear discriminant analysis (LDA) could be applied to distinguish site-specific differences; linear discriminant function (LDF) was also applied to classify sites. The sampled feathers varied in their chemical exposure patterns depending on whether they were sourced from one site associated with heavy metal exposure or the other which suggested high organic pollutant exposures. CCA of chemical and spectral data showed a correlation between spectral signatures and chemical exposure. PCA-LDA readily distinguished feathers from the two different sites. Discriminating alterations were identified and these were associated with pr
- Published
- 2012
45. A spectral phenotype of oncogenic human papillomavirus-infected exfoliative cervical cytology distinguishes women based on age
- Author
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Kerns, Jemma, Cheung, Karen T., Martin, Cara, O'Leary, John J., Prendiville, Walter, Martin-Hirsch, Pierre L., Martin, Francis L, Kerns, Jemma, Cheung, Karen T., Martin, Cara, O'Leary, John J., Prendiville, Walter, Martin-Hirsch, Pierre L., and Martin, Francis L
- Abstract
BACKGROUND: Human papillomavirus (HPV) is a sexually-transmitted infection associated with cervical cancer. Of over 100 HPV types identified, 13 are high-risk oncogenic. In unvaccinated women worldwide, the incidence of cervical cancer from HPV16 and HPV18 will remain. Cervical cytology can be graded from normal (atypia-free) to low-grade to high-grade. Infrared (IR) spectroscopy is a non-destructive technique that allows the acquisition of a biochemical-cell fingerprint based on vibrational states of chemical bonds. METHODS: Exfoliative cervical cytology specimens (n=147) were retrieved, graded by a cytologist and HPV-tested/genotyped using hybrid capture 2 and the Roche HPV Linear Array. Additionally, the spectral signatures of cervical cell lines C33A, HeLa and SiHa were examined. After washing, cellular material was transferred to low-E glass slides and interrogated using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. Given the complex nature of the dataset consisting of thousands of variables (wavenumbers), we used multivariate analysis for data reduction and information retrieval. Principal component analysis coupled with linear discriminant analysis (PCA-LDA) generated a visual representation of the data (scores plot) and, identification of the wavenumbers and consequent biochemical entities responsible for segregation (loadings plot). RESULTS: Immortalised cell lines were readily distinguishable from each other. It was difficult to segregate categories of cytology associated with HPV infection types. However, in low-grade cytology infected with high-risk oncogenic HPV16 or HPV18, it was possible to segregate women based on whether they were aged 20-29years vs. 30-39years. CONCLUSIONS: Our findings suggest a spectral phenotype in exfoliative cervical cytology associated with transient vs. persistent HPV infection.
- Published
- 2010
46. Discrimination of human stem cells by photothermal microspectroscopy
- Author
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Grude, Olaug, Nakamura, Takahiro, Hammiche, Azzedine, Bentley, Adam J., Martin, Francis L, Pollock, Hubert M., Kinoshita, Shigeru, Fullwood, Nigel J., Grude, Olaug, Nakamura, Takahiro, Hammiche, Azzedine, Bentley, Adam J., Martin, Francis L, Pollock, Hubert M., Kinoshita, Shigeru, and Fullwood, Nigel J.
- Abstract
Stem cells have great potential in clinical medicine. Sensitive methods for stem cell identification are a requirement for the development of medical interventions involving these cells. To date, a definitive stem cell marker has not been discovered. We are exploring the use of photothermal microspectroscopy (PTMS) for the purpose of stem cell characterisation and identification in human corneal epithelium. PTMS measures heat fluctuations associated with infrared radiation absorption. The technique is advantageous over existing Fourier transform infrared (FTIR) spectroscopy methods in having a spatial resolution which is not diffraction limited, thus allowing examination at a sub-cellular scale. PTMS measurements are unaffected by IR opacity of the sample, giving the method a further edge in comparison to FTIR spectroscopy. We show that PTMS spectra can be used for the characterisation of stem cells and differentiated cells in the human corneal stem cell model. We demonstrate for the first time that PTMS spectra derived from these cell types segregate into separate data clusters after principal component analysis. The predominant wavenumbers responsible for this separation appear to be associated with nucleic acid structure and function. PTMS offers great promise as a technique for stem cell identification in tissue samples where spatial resolution at the cellular scale or better is required. (C) 2008 Elsevier B.V. All rights reserved.
- Published
- 2009
47. Non-contact micro-cantilevers detect photothermally induced vibrations that can segregate different categories of exfoliative cervical cytology.
- Author
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Hammiche, Azzedine, Walsh, Michael J., Pollock, Hubert M., Martin-Hirsch, Pierre L., Martin, Francis L, Hammiche, Azzedine, Walsh, Michael J., Pollock, Hubert M., Martin-Hirsch, Pierre L., and Martin, Francis L
- Abstract
We implemented a non-contact photo-thermo-mechanical recording method whereby a silicon nitride atomic force microscopy cantilever is placed several micrometer above the surface of samples. Samples were illuminated with infrared (IR) radiation after which, cantilever mechanical vibrations were optically sensed. Following spectrometric acquisition and Fourier transformation, true IR absorption spectra were obtained. With multivariate analysis, segregation between different categories of exfoliative cervical cytology was obtained. This approach points towards the implementation of a novel near-field system that allows IR spectral analysis without probe contamination.
- Published
- 2007
48. IR microspectroscopy: potential applications in cervical cancer screening.
- Author
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Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., German, Matthew J., Singh, Maneesh, Pollock, Hubert M., Hammiche, Azzedine, Kyrgiou, Maria, Stringfellow, Helen F., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
- Abstract
Screening exfoliative cytology for early dysplastic cells reduces incidence and mortality from squamous carcinoma of the cervix. In the developed world, screening programmes have adopted a 3?5 years recall system. In its absence, cervical cancer would be the second most common female cancer in these regions; instead, it is currently eleventh. However, there exist a number of limitations to the smear test even given the removal of contaminants using liquid-based cytology. It is prohibitively expensive, labour-intensive and subject to inaccuracies that give rise to significant numbers of false negatives. There remains a need for novel approaches to allow efficient and objective interrogation of exfoliative cytology. Methods that variously exploit infrared (IR) microspectroscopy are one possibility. Using IR microspectroscopy, an integrated ?biochemical-cell fingerprint? of the lipid, protein and carbohydrate composition of a biomolecular entity may be derived in the form of a spectrum via vibrational transitions of individual chemical bonds. Powerful statistical approaches (e.g. principal component analysis) now facilitate the interrogation of large amounts of spectroscopic data to allow the extraction of what may be small but extremely significant biomarker differences between disease-free and pre-malignant or malignant samples. An increasing wealth of literature points to the ability of IR microspectroscopy to allow the segregation of cells based on their disease status. We review the current evidence supporting its diagnostic potential in cancer biology.
- Published
- 2007
49. ATR microspectroscopy with multivariate analysis segregates grades of exfoliative cervical cytology.
- Author
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Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., Martin, Francis L, Walsh, Michael J., Singh, Maneesh N., Pollock, Hubert M., Cooper, Leanne J., German, Matthew J., Stringfellow, Helen F., Fullwood, Nigel J., Paraskevaidis, Evangelos, Martin-Hirsch, Pierre L., and Martin, Francis L
- Abstract
Although cervical cancer screening in the UK has led to reductions in the incidence of invasive disease, this programme remains flawed. We set out to examine the potential of infrared (IR) microspectroscopy to allow the profiling of cellular biochemical constituents associated with disease progression. Attenuated total reflection-Fourier Transform IR (ATR) microspectroscopy was employed to interrogate spectral differences between samples of exfoliative cervical cytology collected into liquid based cytology (LBC). These were histologically characterised as normal (n = 5), low-grade (n = 5), high-grade (n = 5) or severe dyskaryosis (? carcinoma) (n = 5). Examination of resultant spectra was coupled with principal component analysis (PCA) and subsequent linear discriminant analysis (LDA). The interrogation of LBC samples using ATR microspectroscopy with PCA?LDA facilitated the discrimination of different categories of exfoliative cytology and allowed the identification of potential biomarkers of abnormality; these occurred prominently in the IR spectral region 1200 cm?1?950 cm?1 consisting of carbohydrates, phosphate, and glycogen. Shifts in the centroids of amide I (≈1650 cm?1) and II (≈1530 cm?1) absorbance bands, indicating conformational changes to the secondary structure of intracellular proteins and associated with increasing disease progression, were also noted. This work demonstrates the potential of ATR microspectroscopy coupled with multivariate analysis to be an objective alternative to routine cytology.
- Published
- 2007
50. Short and medium chain length chlorinated paraffins in UK human milk fat
- Author
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Thomas, Gareth O., Farrar, David, Braekvelt, Eric, Stern, Gary, Kalantzi, Olga L., Martin, Francis L, Jones, Kevin C., Thomas, Gareth O., Farrar, David, Braekvelt, Eric, Stern, Gary, Kalantzi, Olga L., Martin, Francis L, and Jones, Kevin C.
- Abstract
Chlorinated paraffins (also called polychlorinated n-alkanes — PCAs) are a class of industrial chemicals comprising chlorinated straight chain hydrocarbons. They have a wide range of applications and are now found in a range of environmental compartments. We analysed a total of 25 human milk-fat samples, donated by 18 individuals from the urban London and more rural Lancaster areas in the UK, for short chain PCAs (C10?C13 sPCAs) and medium chain PCAs (C14?C17 mPCAs), using gas chromatography?ECNI high-resolution mass spectrometry. Our study confirms that trace quantities of PCAs can reach human milk-fat. sPCAs were detected in all but four samples, while mPCAs were detected in all samples. The median sPCA concentration was 180 ng/g fat (range of 49 to 820 ng/g fat — detected values only) and the median mPCA concentration was 21 ng/g fat (range of 6.2 to 320 ng/g fat). No differences were noted in ranges of observed values for either sPCAs or mPCAs between samples from London and Lancaster. Most samples also exhibited similar patterns of sPCAs and mPCAs. One sample exhibited a different pattern for sPCAs and mPCAs, an observation that may be related to differences in exposure or biological factors for this individual.
- Published
- 2006
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