Towards novel compact laser sources for non-invasive diagnostics and treatment

An important field of application of lasers is biomedical optics. Here, they offer great utility for diagnosis, therapy and surgery. For the development of novel methods of laser-based biomedical diagnostics careful study of light propagation in biological tissues is necessary to enhance our understanding of the optical measurements undertaken, increase research and development capacity and the diagnostic reliability of optical technologies. Ultimately, fulfilling these requirements will increase uptake in clinical applications of laser based diagnostics and therapeutics. To address these challenges informative biomarkers relevant to the biological and physiological function or disease state of the organism must be selected. These indicators are the results of the analysis of tissues and cells, such as blood. For non-invasive diagnostics peripheral blood, cells and tissue can potentially provide comprehensive information on the condition of the human organism. A detailed study of the light scattering and absorption characteristics can quickly detect physiological and morphological changes in the cells due to thermal, chemical, antibiotic treatments, etc [1-5]. The selection of a laser source to study the structure of biological particles also benefits from the fact that gross pathological changes are not induced and diagnostics make effective use of the monochromatic directional coherence properties of laser radiation.

Changes in autofluorescence based organoid model of muscle invasive urinary bladder cancer

Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients.

Water Uptake Patterns of an Invasive Exotic Plant in Coastal Saline Habitats

Schinus terebinthifolius Raddi (Schinus) is one of the most widely found woody exotic species in South Florida. This exotic is distributed across environments with different hydrologic regimes, from upland pine forests to the edges of sawgrass marshes and into saline mangrove forests. To determine if this invasive exotic had different physiological attributes compared to native species in a coastal habitat, we measured predawn xylem water potentials (Ψ), oxygen stable isotope signatures (δ18O), and sodium (Na+) and potassium (K+) contents of sap water from plants within: (1) a transition zone (between a mangrove forest and upland pineland) and (2) an upland pineland in Southwest Florida. Under dynamic salinity and hydrologic conditions, Ψ of Schinus appeared less subject to fluctuations caused by seasonality when compared with native species. Although stem water δ18O values could not be used to distinguish the depth of Schinus and native species' water uptake in the transition zone, Ψ and sap Na+/K+ patterns showed that Schinus was less of a salt excluder relative to the native upland species during the dry season. This exotic also exhibited Na+/K+ ratios similar to the mangrove species, indicating some salinity tolerance. In the upland pineland, Schinus water uptake patterns were not significantly different from those of native species. Differences between Schinus and native upland species, however, may provide this exotic an advantage over native species within mangrove transition zones.

Imunoexpressão da proteína endonuclease apurínica/apurimidínica (APE-1) em adenomas pleomórficos e carcinomas ex-adenomas pleomórficos

Introduction: Apurinic/Apyrimidinic Endonuclease 1 (APE-1) is an essential protein for DNA base excision repair (BER) pathway and regulation of redox activities. The ability of malignant cells to recognize and repair DNA damage is an important mechanism for tumor survival, and recent studies suggest that APE-1 overexpression is related to poor prognosis in some tumors. Purpose: To analyze the immunoreactivity of APE-1 in Pleomorphic Adenomas (PA) and Carcinomas Ex Pleomorphic Adenomas (CaExPA) of salivary glands. Materials and Methods: A total of 49 tumors fixed in formalin and embedded in paraffin (33 PA and 16 CaExPA) underwent immunohistochemical study by the immunoperoxidase technique. APE-1 immunoreactivity was evaluated quantitatively by the percentage of immunopositive cells. For statistical analysis a significance level of 5% (p≤ 0.05) was adopted. Results: All cases of PA and CaExPA (n=49) were positive for APE-1, however, there was a higher expression in CaExPA, with statistically significant difference (p<0.001). There was no association between APE-1 expression and tumors of major or minor salivary gland, however, not encapsulated PA (median expression = 54.2%) showed higher expression when compared to encapsulated tumors (p=0.02). APE-1 overexpression was found mainly in cases of CaExAP with lymph node metastasis (median expression = 90.3% - p=0.002) and invasive pattern (median expression = 89.9% - p=0.003), when compared to cases without metastasis and intracapsular pattern. Conclusion: This study suggests that APE-1 is deregulated in the studied tumors. The increased expression of APE-1 is associated with the absence of complete capsule in PA and it is associated with more aggressive behavior in CaExPA.

Imunoexpressão da proteína endonuclease apurínica/apurimidínica (APE-1) em adenomas pleomórficos e carcinomas ex-adenomas pleomórficos

Introduction: Apurinic/Apyrimidinic Endonuclease 1 (APE-1) is an essential protein for DNA base excision repair (BER) pathway and regulation of redox activities. The ability of malignant cells to recognize and repair DNA damage is an important mechanism for tumor survival, and recent studies suggest that APE-1 overexpression is related to poor prognosis in some tumors. Purpose: To analyze the immunoreactivity of APE-1 in Pleomorphic Adenomas (PA) and Carcinomas Ex Pleomorphic Adenomas (CaExPA) of salivary glands. Materials and Methods: A total of 49 tumors fixed in formalin and embedded in paraffin (33 PA and 16 CaExPA) underwent immunohistochemical study by the immunoperoxidase technique. APE-1 immunoreactivity was evaluated quantitatively by the percentage of immunopositive cells. For statistical analysis a significance level of 5% (p≤ 0.05) was adopted. Results: All cases of PA and CaExPA (n=49) were positive for APE-1, however, there was a higher expression in CaExPA, with statistically significant difference (p<0.001). There was no association between APE-1 expression and tumors of major or minor salivary gland, however, not encapsulated PA (median expression = 54.2%) showed higher expression when compared to encapsulated tumors (p=0.02). APE-1 overexpression was found mainly in cases of CaExAP with lymph node metastasis (median expression = 90.3% - p=0.002) and invasive pattern (median expression = 89.9% - p=0.003), when compared to cases without metastasis and intracapsular pattern. Conclusion: This study suggests that APE-1 is deregulated in the studied tumors. The increased expression of APE-1 is associated with the absence of complete capsule in PA and it is associated with more aggressive behavior in CaExPA.

Potential impact of invasive anuran species in western Newfoundland

Successful dispersal and establishment of invasive anurans (frogs and toads) may be influenced by competitive exclusion and/or niche differentiation with competing species. I investigated the dispersal of anurans in western Newfoundland using anuran calling surveys and pond-edge visual encounter surveys. The Mink Frog, Lithobates septentrionalis, had dispersed ~50 km northeast from the original (2001) discovery location and ~34 km southwest; displaying spatial separation from Green Frogs, Lithobates clamitans, at landscape and local scales. Visual encounter surveys did not reveal any correlation between adult Mink Frogs and odonate competitors. Additionally, I assessed the impact of varying tadpole densities on removal of epilithic periphyton by providing epilithon covered substrates for American Toad, Anaxyrus americanus, tadpoles raised in laboratory or field enclosures. Higher tadpole densities resulted in smaller tadpoles that removed more periphyton from substrates. As anuran population ranges expand, there may be effects on ecological resources for vertebrate and invertebrate competitors.

Rate of exposure of a sentinel species, invasive American mink (Neovison vison) in Scotland, to anticoagulant rodenticides

Open Access funded by Natural Environment Research Council Acknowledgements Field sample collection was funded by NERC grants NE/E006434/1 and NE/J01396X/1 to XL and a Marie Curie FP7-PEOPLE-2011-IEF 300288-grant to YM. We thank the Scottish Mink Initiative, staff, funders and multiple mink volunteers for the continued effort, samples and data. Also to Eduardo Salazar Villaverde for his assistance in the preparation of figures in early drafts of this manuscript, and Professor Colin Prescott (Reading University) for comments on the biochemistry of ARs. Finally, to Kenneth McNeill for providing data on farm sizes and distributions.

Immunopathogénèse de la candidose oropharyngée chez la souris transgénique exprimant le génome du VIH-1

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats.

Immunopathogénèse de la candidose oropharyngée chez la souris transgénique exprimant le génome du VIH-1

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Predicting the Dispersal Potential of an Invasive Polychaete Pest along a Complex Coastal Biome

Boccardia proboscidea is a recently introduced polychaete in South Africa where it is a notorious pest of commercially reared abalone. Populations were originally restricted to abalone farms but a recent exodus into the wild at some localities has raised conservation concerns due to the species’ invasive status in other parts of the world. Here, we assessed the dispersal potential of B. proboscidea by using a population genetic and oceanographic modeling approach. Since the worm is in its incipient stages of a potential invasion, we used the closely related Polydora hoplura as a proxy due its similar reproductive strategy and its status as a pest of commercially reared oysters in the country. Populations of P. hoplura were sampled from seven different localities and a section of the mtDNA gene, Cyt b and the intron ATPSa was amplified. A high resolution model of the coastal waters around southern Africa was constructed using the Regional Ocean Modeling System. Larvae were represented by passive drifters that were deployed at specific points along the coast and dispersal was quantified after a 12-month integration period. Our results showed discordance between the genetic and modeling data. There was low genetic structure (Φ = 0.04 for both markers) and no geographic patterning of mtDNA and nDNA haplotypes. However, the dispersal model found limited connectivity around Cape Point—a major phylogeographic barrier on the southern African coast. This discordance was attributed to anthropogenic movement of larvae and adult worms due to vectors such as aquaculture and shipping. As such, we hypothesized that cryptic dispersal could be overestimating genetic connectivity. Though wild populations of B. proboscidea could become isolated due to the Cape Point barrier, anthropogenic movement may play the critical role in facilitating the dispersal and spread of this species on the southern African coast.

Predicting the Dispersal Potential of an Invasive Polychaete Pest along a Complex Coastal Biome

Boccardia proboscidea is a recently introduced polychaete in South Africa where it is a notorious pest of commercially reared abalone. Populations were originally restricted to abalone farms but a recent exodus into the wild at some localities has raised conservation concerns due to the species’ invasive status in other parts of the world. Here, we assessed the dispersal potential of B. proboscidea by using a population genetic and oceanographic modeling approach. Since the worm is in its incipient stages of a potential invasion, we used the closely related Polydora hoplura as a proxy due its similar reproductive strategy and its status as a pest of commercially reared oysters in the country. Populations of P. hoplura were sampled from seven different localities and a section of the mtDNA gene, Cyt b and the intron ATPSa was amplified. A high resolution model of the coastal waters around southern Africa was constructed using the Regional Ocean Modeling System. Larvae were represented by passive drifters that were deployed at specific points along the coast and dispersal was quantified after a 12-month integration period. Our results showed discordance between the genetic and modeling data. There was low genetic structure (Φ = 0.04 for both markers) and no geographic patterning of mtDNA and nDNA haplotypes. However, the dispersal model found limited connectivity around Cape Point—a major phylogeographic barrier on the southern African coast. This discordance was attributed to anthropogenic movement of larvae and adult worms due to vectors such as aquaculture and shipping. As such, we hypothesized that cryptic dispersal could be overestimating genetic connectivity. Though wild populations of B. proboscidea could become isolated due to the Cape Point barrier, anthropogenic movement may play the critical role in facilitating the dispersal and spread of this species on the southern African coast.

Contrasting global genetic patterns in two biologically similar, widespread and invasive Ciona species (Tunicata, Ascidiacea)

Human-mediated dispersal interplays with natural processes and complicates understanding of the biogeographical history of species. This is exemplified by two invasive tunicates, Ciona robusta (formerly Ciona intestinalis type A) and C. intestinalis (formerly Ciona intestinalis type B), globally distributed and sympatric in Europe. By gathering new mitochondrial sequences that were merged with published datasets, we analysed genetic patterns in different regions, with a focus on 1) their sympatric range and 2) allopatric populations in N and S America and southern Europe. In the sympatric range, the two species display contrasting genetic diversity patterns, with low polymorphism in C. robusta supporting the prevalent view of its recent introduction. In the E Pacific, several genetic traits support the non-native status of C. robusta. However, in the NE Pacific, this appraisal requires a complex scenario of introduction and should be further examined supported by extensive sampling efforts in the NW Pacific (putative native range). For C. intestinalis, Bayesian analysis suggested a natural amphi-North Atlantic distribution, casting doubt on its non-native status in the NW Atlantic. This study shows that both natural and human-mediated dispersal have influenced genetic patterns at broad scales; this interaction lessens our ability to confidently ascertain native vs. non-native status of populations, particularly of those species that are globally distributed.