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Diet, cell signalling, and tumourigenesis in multiple intestinal neoplasia mice

The incidence of colon cancer is high in Western societies, and in Finland it is among the three most common cancer types in both females and males. Environmental factors, including diet, affect colon cancer development. During the last few years, a vast amount of new, functional foods have been introduced to the consumers. Several products are already available that are marketed as promoting intestinal health. To be able to reliably call a dietary compound a chemopreventive substance it is of fundamental importance to understand the mechanism by which it affects tumour formation and the integrity of the epithelial cells. In this thesis, three different dietary compounds were studied in an experimental model of colon cancer. Inulin is a non-digestible fibre found naturally in chicory roots, artichokes and onions, amongst others. Nowadays it is widely used as an added dietary fibre in several food products. Conjugated linoleic acid (CLA) is a conjugated form of the fatty acid linoleic acid. CLA is formed by bacterial fermentation of linoleic acid in the rumen of cows and other ruminants. Concomitantly, it can naturally be found in milk and meat of ruminants. White currant is a colourless berry low in phenolic compounds that are believed to prevent cancer formation. Contrary to what was expected, inulin and the conjugated linoleic acid isomer trans-10, cis-12, were tumour growth promoting dietary constituents when fed to Min mice. Both diets decreased the NF-kappaB levels in the mucosa, but physiological adenoma development did not affect NF-kappaB. Diet altered beta-catenin and p53 signalling in the adenomas, confirming their involvement in adenoma growth. White currant, on the other hand, was chemopreventive, despite its low contents of phenolic compounds. The chemopreventive effect was accompanied by increased p53 levels in the mucosa, and decreased beta-catenin and NF-kappaB levels in the adenoma. This could explain the reduced adenoma number and size. The results underline the importance of carefully testing new dietary compounds in different settings to reliably confirm their health benefits. In this study two compounds that are consumed and believed to add to our health proved to be cancer promotive. A berry with low phenolic contents, on the other hand, was chemopreventive.

An economical, adaptable and user-friendly drip-perfusion bioreactor system designed for in vitro three dimensional cell culturing

This research project investigated a bioreactor system capable of high density cell growth intended for use in regenerative medicine and protein production. The bioreactor was based on a drip-perfusion concept and constructed with minimal costs, readily available components, and straightforward processes for usage. This study involved the design, construction, and testing of the bioreactor where the results showed promising three dimensional cell growth within a polymer structure. The accessibility of this equipment and the capability of high density, three dimensional cell growth would be suitable for future research in pharmaceutical drug manufacturing, and human organ and tissue regeneration.

Silica vesicles as nanocarriers and adjuvants for generating both antibody and T-cell mediated immune resposes to Bovine Viral Diarrhoea Virus E2 protein

Bovine Viral Diarrhoea Virus (BVDV) is widely distributed in cattle industries and causes significant economic losses worldwide annually. A limiting factor in the development of subunit vaccines for BVDV is the need to elicit both antibody and T-cell-mediated immunity as well as addressing the toxicity of adjuvants. In this study, we have prepared novel silica vesicles (SV) as the new generation antigen carriers and adjuvants. With small particle size of 50 nm, thin wall (similar to 6 nm), large cavity (similar to 40 nm) and large entrance size (5.9 nm for SV-100 and 16 nm for SV-140), the SV showed high loading capacity (similar to 250 mu g/mg) and controlled release of codon-optimised E2 (oE2) protein, a major immunogenic determinant of BVDV. The in vivo functionality of the system was validated in mice immunisation trials comparing oE2 plus Quil A (50 mu g of oE2 plus 10 mu g of Quil A, a conventional adjuvant) to the oE2/SV-140 (50 mu g of oE2 adsorbed to 250 mu g of SV-140) or oE2/SV-140 together with 10 mu g of Quil A. Compared to the oE2 plus Quil A, which generated BVDV specific antibody responses at a titre of 10(4), the oE2/SV-140 group induced a 10 times higher antibody response. In addition, the cell-mediated response, which is essential to recognise and eliminate the invading pathogens, was also found to be higher [1954-2628 spot forming units (SFU)/million cells] in mice immunised with oE2/SV-140 in comparison to oE2 plus Quil A (512-1369 SFU/million cells). Our study has demonstrated that SV can be used as the next-generation nanocarriers and adjuvants for enhanced veterinary vaccine delivery. (C) 2014 Elsevier Ltd. All rights reserved.

Electrophoretic mobility of cell nuclei (EMN index) as a biomarker of the biological aging process: Considering the association between EMN index and age

The present study examined whether a specific property of cell microstructures may be useful as a biomarker of aging. Specifically, the association between age and changes of cellular structures reflected in electrophoretic mobility of cell nuclei index (EMN index) values across the adult lifespan was examined. This report considers findings from cross sections of females (n = 1273) aged 18–98 years, and males (n = 506) aged 19–93 years. A Biotest apparatus was used to perform intracellular microelectrophoresis on buccal epithelial cells collected from each individual. EMN index was calculated on the basis of the number of epithelial cells with mobile nuclei in reference to the cells with immobile nuclei per 100 cells. Regression analyses indicated a significant negative association between EMN index value and age for men (r = −0.71, p < 0.001) and women (r = −0.60, p < 0.001); demonstrating a key requirement that must be met by a biomarker of aging. The strength of association observed between EMN index and age for both men and women was encouraging and supports the potential use of EMN index for determining a biological age of an individual (or a group). In this study, a new attempt of complex explanation of cellular mechanisms contributing to age related changes of the EMN index was made. In this study, a new attempt of complex explanation of cellular mechanisms contributing to age related changes of the EMN index was made. EMN index has demonstrated potential to meet criteria proposed for biomarkers of aging and further investigations are necessary.

Studies on the Mechanism of Action of Miconazole: Effect of Miconazole on Respiration and Cell Permeability of Candida albicans

The antifungal drug, miconazole nitrate, inhibits the growth of several species of Candida. Candida albicans, one of the pathogenic species, was totally inhibited at a concentration of approximately 10 μg/ml. Endogenous respiration was unaffected by the drug at a concentration as high as 100 μg/ml, whereas exogenous respiration was markedly sensitive and inhibited to an extent of 85%. The permeability of the cell membrane was changed as evidenced by the leakage of 260-nm absorbing materials, amino acids, proteins, and inorganic cations. The results we present clearly show that the drug alters the cellular permeability, and thus the exogenous respiration becomes sensitive to the drug.

Ant colony optimization for reporting cell planning in mobile computing using selective paging strategy

Location management problem that arise in mobile computing networks is addressed. One method used in location management is to designate sonic of the cells in the network as "reporting cells". The other cells in the network are "non-reporting cells". Finding an optimal set of reporting cells (or reporting cell configuration) for a given network. is a difficult combinatorial optimization problem. In fact this is shown to be an NP-complete problem. in an earlier study. In this paper, we use the selective paging strategy and use an ant colony optimization method to obtain the best/optimal set of reporting cells for a given a network.

Mathematical modelling of human corneal oxygenation and cell kinetics in corneal epithelial wound healing

Healthy transparent cornea depends upon the regulation of fluid, nutrient and oxygen transport through the tissue to sustain cell metabolism and other critical processes for normal functioning. This research considers the corneal geometry and investigates oxygen distribution using a two-dimensional Monod kinetic model, showing that previous studies make assumptions that lead to predictions of near-anoxic levels of oxygen tension in the limbal regions of the cornea. It also considers the comparison of experimental spatial and temporal data with the predictions of novel mathematical models with respect to distributed mitotic rates during corneal epithelial wound healing.

Assessment of conjunctival goblet cell density using laser scanning confocal microscopy versus impression cytology

Purpose To determine the association between conjunctival goblet cell density (GCD) assessed using in vivo laser scanning confocal microscopy and conjunctival impression cytology in a healthy population. Methods Ninety (90) healthy participants undertook a validated 5-item dry eye questionnaire, non-invasive tear film break-up time measurement, ocular surface fluorescein staining and phenol red thread test. These tests where undertaken to diagnose and exclude participants with dry eye. The nasal bulbar conjunctiva was imaged using laser scanning confocal microscopy (LSCM). Conjunctival impression cytology (CIC) was performed in the same region a few minutes later. Conjunctival goblet cell density was calculated as cells/mm2. Results There was a strong positive correlation of conjunctival GCD between LSCM and CIC (ρ = 0.66). Conjunctival goblet cell density was 475 ± 41 cells/mm2 and 466 ± 51 cells/mm2 measured by LSCM and CIC, respectively. Conclusions The strong association between in vivo and in vitro cellular analysis for measuring conjunctival GCD suggests that the more invasive CIC can be replaced by the less invasive LSCM in research and clinical practice.

Non-cellulosic cell wall polysaccharides are subject to genotype × environment effects in sorghum (Sorghum bicolor) grain

Sorghum is a staple food for half a billion people and, through growth on marginal land with minimal inputs, is an important source of feed, forage and increasingly, biofuel feedstock. Here we present information about non-cellulosic cell wall polysaccharides in a diverse set of cultivated and wild Sorghum bicolor grains. Sorghum grain contains predominantly starch (64–76) but is relatively deficient in other polysaccharides present in wheat, oats and barley. Despite overall low quantities, sorghum germplasm exhibited a remarkable range in polysaccharide amount and structure. Total (1,3;1,4)-β-glucan ranged from 0.06 to 0.43 (w/w) whilst internal cellotriose:cellotetraose ratios ranged from 1.8 to 2.9:1. Arabinoxylan amounts fell between 1.5 and 3.6 (w/w) and the arabinose:xylose ratio, denoting arabinoxylan structure, ranged from 0.95 to 1.35. The distribution of these and other cell wall polysaccharides varied across grain tissues as assessed by electron microscopy. When ten genotypes were tested across five environmental sites, genotype (G) was the dominant source of variation for both (1,3;1,4)-β-glucan and arabinoxylan content (69–74), with environment (E) responsible for 5–14. There was a small G × E effect for both polysaccharides. This study defines the amount and spatial distribution of polysaccharides and reveals a significant genetic influence on cell wall composition in sorghum grain.

Studies on the Mechanism of Action of Miconazole: Effect of Miconazole on Respiration and Cell Permeability of Candida albicans

The antifungal drug, miconazole nitrate, inhibits the growth of several species of Candida. Candida albicans, one of the pathogenic species, was totally inhibited at a concentration of approximately 10 µg/ml. Endogenous respiration was unaffected by the drug at a concentration as high as 100 µg/ml, whereas exogenous respiration was markedly sensitive and inhibited to an extent of 85%. The permeability of the cell membrane was changed as evidenced by the leakage of 260-nm absorbing materials, amino acids, proteins, and inorganic cations. The results we present clearly show that the drug alters the cellular permeability, and thus the exogenous respiration becomes sensitive to the drug.

Cross Talk between Receptor Guanylyl Cyclase C and c-src Tyrosine Kinase Regulates Colon Cancer Cell Cytostasis

Increased activation of c-src seen in colorectal cancer is an indicator of a poor clinical prognosis, suggesting that identification of downstream effectors of c-src may lead to new avenues of therapy. Guanylyl cyclase C (GC-C) is a receptor for the gastrointestinal hormones guanylin and uroguanylin and the bacterial heat-stable enterotoxin. Though activation of GC-C by its ligands elevates intracellular cyclic GMP (cGMP) levels and inhibits cell proliferation, its persistent expression in colorectal carcinomas and occult metastases makes it a marker for malignancy. We show here that GC-C is a substrate for inhibitory phosphorylation by c-src, resulting in reduced ligand-mediated cGMP production. Consequently, active c-src in colonic cells can overcome GC-C-mediated control of the cell cycle. Furthermore, docking of the c-src SH2 domain to phosphorylated GC-C results in colocalization and further activation of c-src. We therefore propose a novel feed-forward mechanism of activation of c-src that is induced by cross talk between a receptor GC and a tyrosine kinase. Our findings have important implications in understanding the molecular mechanisms involved in the progression and treatment of colorectal cancer.

Efficient eucalypt cell wall deconstruction and conversion for sustainable lignocellulosic biofuels

In order to meet the world’s growing energy demand and reduce the impact of greenhouse gas emissions resulting from fossil fuel combustion, renewable plant-based feedstocks for biofuel production must be considered. The first-generation biofuels, derived from starches of edible feedstocks, such as corn, create competition between food and fuel resources, both for the crop itself and the land on which it is grown. As such, biofuel synthesized from non-edible plant biomass (lignocellulose) generated on marginal agricultural land will help to alleviate this competition. Eucalypts, the broadly defined taxa encompassing over 900 species of Eucalyptus, Corymbia, and Angophora are the most widely planted hardwood tree in the world, harvested mainly for timber, pulp and paper, and biomaterial products. More recently, due to their exceptional growth rate and amenability to grow under a wide range of environmental conditions, eucalypts are a leading option for the development of a sustainable lignocellulosic biofuels. However, efficient conversion of woody biomass into fermentable monomeric sugars is largely dependent on pretreatment of the cell wall, whose formation and complexity lend itself toward natural recalcitrance against its efficient deconstruction. A greater understanding of this complexity within the context of various pretreatments will allow the design of new and effective deconstruction processes for bioenergy production. In this review, we present the various pretreatment options for eucalypts, including research into understanding structure and formation of the eucalypt cell wall.

Drug discovery approaches utilizing three-dimensional cell culture

Historically, two-dimensional (2D) cell culture has been the preferred method of producing disease models in vitro. Recently, there has been a move away from 2D culture in favor of generating three-dimensional (3D) multicellular structures, which are thought to be more representative of the in vivo environment. This transition has brought with it an influx of technologies capable of producing these structures in various ways. However, it is becoming evident that many of these technologies do not perform well in automated in vitro drug discovery units. We believe that this is a result of their incompatibility with high-throughput screening (HTS). In this study, we review a number of technologies, which are currently available for producing in vitro 3D disease models. We assess their amenability with high-content screening and HTS and highlight our own work in attempting to address many of the practical problems that are hampering the successful deployment of 3D cell systems in mainstream research.

Service Composition on a Mobile Phone

With the recent increase in interest in service-oriented architectures (SOA) and Web services, developing applications with the Web services paradigm has become feasible. Web services are self-describing, platform-independent computational elements. New applications can be assembled from a set of previously created Web services, which are composed together to make a service that uses its components to perform a certain task. This is the idea of service composition. To bring service composition to a mobile phone, I have created Interactive Service Composer for mobile phones. With Interactive Service Composer, the user is able to build service compositions on his mobile phone, consisting of Web services or services that are available from the mobile phone itself. The service compositions are reusable and can be saved in the phone's memory. Previously saved compositions can also be used in new compositions. While developing applications for mobile phones has been possible for some time, the usability of the solutions is not the same as when developing for desktop computers. When developing for mobile phones, the developer has to more carefully consider the decisions he is going to make with the program he is developing. With the lack of processing power and memory, the applications cannot function as well as on desktop PCs. On the other hand, this does not remove the appeal of developing applications for mobile devices.