A matter of taste : genetic and environmental influences on responses to sweetness

Diet is a major player in the maintenance of health and onset of many diseases of public health importance. The food choice is known to be largely influenced by sensory preferences. However, in many cases it is unclear whether these preferences and dietary behaviors are innate or acquired. The aim of this thesis work was to study the extent to which the individual differences in dietary responses, especially in liking for sweet taste, are influenced by genetic factors. Several traits measuring the responses to sweetness and other dietary variables were applied in four studies: in British (TwinsUK) and Finnish (FinnTwin12 and FinnTwin16) twin studies and in a Finnish migraine family study. All the subjects were adults and they participated in chemosensory measurements (taste and smell tests) and filled in food behavior questionnaires. Further, it was studied, whether the correlations among the variables are mediated by genetic or environmental factors and where in the genome the genes influencing the heritable traits are located. A study of young adult Finnish twins (FinnTwin16, n=4388) revealed that around 40% of the food use is attributable to genetic factors and that the common, childhood environment does not affect the food use even shortly after moving from the parents home. Both the family study (n=146) and the twin studies (British twins, n=663) showed that around half of the variation in the liking for sweetness is inherited. The same result was obtained both by the chemosensory measurements (heritability 41-49%) and the questionnaire variables (heritability 31-54%). By contrast, the intensity perception of sweetness or the responses to saltiness were not influenced by genetic factors. Further, a locus influencing the use-frequency of sweet foods was identified on chromosome 16p. A closer examination of the relationships among the variables based on 663 British twins revealed that several genetic and environmental correlations exist among the different measures of liking for sweetness. However, these correlations were not very strong (range 0.06-0.55) implying that the instruments used measure slightly different aspects of the phenomenon. In addition, the assessment of the associations among responses to fatty foods, dieting behaviors, and body mass index in twin populations (TwinsUK n=1027 and FinnTwin12 n=299) showed that the dieting behaviors (cognitive restraint, uncontrolled eating, and emotional eating) mediate the relationship between obesity and diet. In conclusion, the work increased the understanding of the background variables of human eating behavior. Genetic effects were shown to underlie the variation of many dietary traits, such as liking for sweet taste, use of sweet foods, and dieting behaviors. However, the responses to salty taste were shown to be mainly determined by environmental factors and thus should more easily be modifiable by dietary education, exposure, and learning than sweet taste preferences. Although additional studies are needed to characterize the genetic element located on chromosome 16 that influences the use-frequency of sweet foods, the results underline the importance of inherited factors on human eating behavior.

Methane in Australian agriculture: current emissions, sources and sinks, and potential mitigation strategies

Methane is a potent greenhouse gas with a global warming potential ∼28 times that of carbon dioxide. Consequently, sources and sinks that influence the concentration of methane in the atmosphere are of great interest. In Australia, agriculture is the primary source of anthropogenic methane emissions (60.4% of national emissions, or 3260kt-1methaneyear-1, between 1990 and 2011), and cropping and grazing soils represent Australia's largest potential terrestrial methane sink. As of 2011, the expansion of agricultural soils, which are ∼70% less efficient at consuming methane than undisturbed soils, to 59% of Australia's land mass (456Mha) and increasing livestock densities in northern Australia suggest negative implications for national methane flux. Plant biomass burning does not appear to have long-term negative effects on methane flux unless soils are converted for agricultural purposes. Rice cultivation contributes marginally to national methane emissions and this fluctuates depending on water availability. Significant available research into biological, geochemical and agronomic factors has been pertinent for developing effective methane mitigation strategies. We discuss methane-flux feedback mechanisms in relation to climate change drivers such as temperature, atmospheric carbon dioxide and methane concentrations, precipitation and extreme weather events. Future research should focus on quantifying the role of Australian cropping and grazing soils as methane sinks in the national methane budget, linking biodiversity and activity of methane-cycling microbes to environmental factors, and quantifying how a combination of climate change drivers will affect total methane flux in these systems.

Lake sediment research as a part of lake management - case studies and implications from southern Finland

In Finland one of the most important current issues in the environmental management is the quality of surface waters. The increasing social importance of lakes and water systems has generated wide-ranging interest in lake restoration and management, concerning especially lakes suffering from eutrophication, but also from other environmental impacts. Most of the factors deteriorating the water quality in Finnish lakes are connected to human activities. Especially since the 1940's, the intensified farming practices and conduction of sewage waters from scattered settlements, cottages and industry have affected the lakes, which simultaneously have developed in to recreational areas for a growing number of people. Therefore, this study was focused on small lakes, which are human impacted, located close to settlement areas and have a significant value for local population. The aim of this thesis was to obtain information from lake sediment records for on-going lake restoration activities and to prove that a well planned, properly focused lake sediment study is an essential part of the work related to evaluation, target consideration and restoration of Finnish lakes. Altogether 11 lakes were studied. The study of Lake Kaljasjärvi was related to the gradual eutrophication of the lake. In lakes Ormajärvi, Suolijärvi, Lehee, Pyhäjärvi and Iso-Roine the main focus was on sediment mapping, as well as on the long term changes of the sedimentation, which were compared to Lake Pääjärvi. In Lake Hormajärvi the role of different kind of sedimentation environments in the eutrophication development of the lake's two basins were compared. Lake Orijärvi has not been eutrophied, but the ore exploitation and related acid main drainage from the catchment area have influenced the lake drastically and the changes caused by metal load were investigated. The twin lakes Etujärvi and Takajärvi are slightly eutrophied, but also suffer problems associated with the erosion of the substantial peat accumulations covering the fringe areas of the lakes. These peat accumulations are related to Holocene water level changes, which were investigated. The methods used were chosen case-specifically for each lake. In general, acoustic soundings of the lakes, detailed description of the nature of the sediment and determinations of the physical properties of the sediment, such as water content, loss on ignition and magnetic susceptibility were used, as was grain size analysis. A wide set of chemical analyses was also used. Diatom and chrysophycean cyst analyses were applied, and the diatom inferred total phosphorus content was reconstructed. The results of these studies prove, that the ideal lake sediment study, as a part of a lake management project, should be two-phased. In the first phase, thoroughgoing mapping of sedimentation patterns should be carried out by soundings and adequate corings. The actual sampling, based on the preliminary results, must include at least one long core from the main sedimentation basin for the determining the natural background state of the lake. The recent, artificially impacted development of the lake can then be determined by short-core and surface sediment studies. The sampling must be focused on the basis of the sediment mapping again, and it should represent all different sedimentation environments and bottom dynamic zones, considering the inlets and outlets, as well as the effects of possible point loaders of the lake. In practice, the budget of the lake management projects of is usually limited and only the most essential work and analyses can be carried out. The set of chemical and biological analyses and dating methods must therefore been thoroughly considered and adapted to the specific management problem. The results show also, that information obtained from a properly performed sediment study enhances the planning of the restoration, makes possible to define the target of the remediation activities and improves the cost-efficiency of the project.

The combined effect of biological control with plant competition on the management of parthenium weed (Parthenium hysterophorus l.)

Parthenium hysterophorus L., (Asteraceae) commonly known as parthenium weed, is a highly invasive plant that has become a problematic weed of pasture lands in Australia and many other countries around the world. For the management of this weed, an integrated approach comprising biological control and plant competition strategies was tested in southern central Queensland. Two competitive pasture plant species (butterfly pea and buffel grass), selected for their high competitive ability, worked successfully with the biological control agent (Epiblema strenuana Walker) to synergistically reduce the biomass of parthenium weed, by between 62 and 69%. In the presence of biological control agent, the corresponding biomass of competitive plants, butterfly pea and buffel grass increased in comparison to when the biological control agent had been excluded, by 15 and 35%, respectively. This suggests that biological control and competitive plants can complement one another to bring about improved management of parthenium weed in Australia. Further, this approach may be adopted in countries where some of the biological control agents are already present including South Africa, Ethiopia, India, Pakistan and Nepal.

Construction of a global map of human gene expression : the process, tools and analysis

This thesis studies human gene expression space using high throughput gene expression data from DNA microarrays. In molecular biology, high throughput techniques allow numerical measurements of expression of tens of thousands of genes simultaneously. In a single study, this data is traditionally obtained from a limited number of sample types with a small number of replicates. For organism-wide analysis, this data has been largely unavailable and the global structure of human transcriptome has remained unknown. This thesis introduces a human transcriptome map of different biological entities and analysis of its general structure. The map is constructed from gene expression data from the two largest public microarray data repositories, GEO and ArrayExpress. The creation of this map contributed to the development of ArrayExpress by identifying and retrofitting the previously unusable and missing data and by improving the access to its data. It also contributed to creation of several new tools for microarray data manipulation and establishment of data exchange between GEO and ArrayExpress. The data integration for the global map required creation of a new large ontology of human cell types, disease states, organism parts and cell lines. The ontology was used in a new text mining and decision tree based method for automatic conversion of human readable free text microarray data annotations into categorised format. The data comparability and minimisation of the systematic measurement errors that are characteristic to each lab- oratory in this large cross-laboratories integrated dataset, was ensured by computation of a range of microarray data quality metrics and exclusion of incomparable data. The structure of a global map of human gene expression was then explored by principal component analysis and hierarchical clustering using heuristics and help from another purpose built sample ontology. A preface and motivation to the construction and analysis of a global map of human gene expression is given by analysis of two microarray datasets of human malignant melanoma. The analysis of these sets incorporate indirect comparison of statistical methods for finding differentially expressed genes and point to the need to study gene expression on a global level.

Structure and Conformation of a Cyclic Tripeptide

MANY cyclic peptides have interesting biological functions and the details of their molecular structure and conformation have been the subject of extensive investigations. Cyclic dipeptides such as diketopiperazine have been synthesised and shown to occur with the peptide units in the cis configuration1,2. In the case of a tripeptide, cyclisation can take place only if all three units are in the cis configuration3. In cyclic peptides with four units also, cis peptides are found4,5. As the number of the peptide units increases, the more stable trans configuration is generally more common6,7. We report here the main results of our X-ray crystallographic investigations of the cyclic tripeptides L-Pro-L-Pro-L-Pro and L-Pro-L-Pro-L-Hyp (hereafter called CTP 1 and CTP 2, respectively). CTP 1 was synthesised by Rothe et al. 8 and its derivatives have been prepared by Blout and his collaborators9.

Bioavailability and toxicity of chemicals in inland waters : the importance of prevailing water chemistry and implications for risk assessment

Physicochemical characterization of freshwater samples from Finland, Sweden, the Netherlands, and Spain revealed that water hardness and pH decreased and the quantity and quality of humic substances changed considerably in this geographical series from south to north. Since the ambient water chemistry may affect the availability of chemicals, the total aqueous concentration of a chemical may be insufficient to predict the bioconcentration, subsequent biological response, and thus risk. In addition, organisms could be affected directly by water quality characteristics. In this context the main objective of this thesis was to investigate the bioavailability of selected ecotoxicologically relevant chemicals (cadmium, benzo(a)pyrene, and pyrene) in various European surface waters and to show the importance of certain water chemistry characteristics in interpreting the bioavailability and toxicity results. The bioavailability of cadmium to Daphnia magna was examined in very soft humic lake water. Humic substances as natural ligands decreased the free and bioavailable proportion of cadmium in soft lake water. As a consequence the uptake rate and the acute toxicity decreased compared with the humic-free reference. When the hardness of humic lake water was artificially elevated, the acute toxicity of cadmium decreased, although the proportion of free cadmium increased. The decreased bioavailability of cadmium in hard water was a result of effective competition for uptake by the hardness cations, especially calcium ions. The protective role of humic substances and water hardness against cadmium toxicity was also observed in Lumbriculus variegatus, although D. magna was more sensitive to cadmium. The bioavailability of two polycyclic aromatic hydrocarbons (PAHs), pyrene and benzo(a)pyrene, was studied in European surface waters of varying water chemistry. Humic substances acted as complexing ligands with both PAHs, but the bioavailability of the more lipophilic benzo(a)pyrene to D. magna was affected more by humic substances than that of pyrene. In addition, not only the quantity of humic substances, but also their quality affected the bioavailability of benzo(a)pyrene. Nevertheless, the humic substances played a protective role in the photo-enhanced toxicity of pyrene under UV-B radiation. Water hardness had no effect on pyrene toxicity. Results indicate that the typical physicochemical characteristics of boreal freshwaters should be considered carefully in local and regional risk assessment of chemicals concerning the Fennoscandian region.

Quarantine and surveillance strategies for plant pathogen detection and control

Incursions of plant pests and diseases pose serious threats to food security, agricultural productivity and the natural environment. One of the challenges in confidently delimiting and eradicating incursions is how to choose from an arsenal of surveillance and quarantine approaches in order to best control multiple dispersal pathways. Anthropogenic spread (propagules carried on humans or transported on produce or equipment) can be controlled with quarantine measures, which in turn can vary in intensity. In contrast, environmental spread processes are more difficult to control, but often have a temporal signal (e.g. seasonality) which can introduce both challenges and opportunities for surveillance and control. This leads to complex decisions regarding when, where and how to search. Recent modelling investigations of surveillance performance have optimised the output of simulation models, and found that a risk-weighted randomised search can perform close to optimally. However, exactly how quarantine and surveillance strategies should change to reflect different dispersal modes remains largely unaddressed. Here we develop a spatial simulation model of a plant fungal-pathogen incursion into an agricultural region, and its subsequent surveillance and control. We include structural differences in dispersal via the interplay of biological, environmental and anthropogenic connectivity between host sites (farms). Our objective was to gain broad insights into the relative roles played by different spread modes in propagating an invasion, and how incorporating knowledge of these spread risks may improve approaches to quarantine restrictions and surveillance. We find that broad heuristic rules for quarantine restrictions fail to contain the pathogen due to residual connectivity between sites, but surveillance measures enable early detection and successfully lead to suppression of the pathogen in all farms. Alternative surveillance strategies attain similar levels of performance by incorporating environmental or anthropogenic dispersal risk in the prioritisation of sites. Our model provides the basis to develop essential insights into the effectiveness of different surveillance and quarantine decisions for fungal pathogen control. Parameterised for authentic settings it will aid our understanding of how the extent and resolution of interventions should suitably reflect the spatial structure of dispersal processes.

Conceptual and statistical modelling of environmental effects in population dynamics

Population dynamics are generally viewed as the result of intrinsic (purely density dependent) and extrinsic (environmental) processes. Both components, and potential interactions between those two, have to be modelled in order to understand and predict dynamics of natural populations; a topic that is of great importance in population management and conservation. This thesis focuses on modelling environmental effects in population dynamics and how effects of potentially relevant environmental variables can be statistically identified and quantified from time series data. Chapter I presents some useful models of multiplicative environmental effects for unstructured density dependent populations. The presented models can be written as standard multiple regression models that are easy to fit to data. Chapters II IV constitute empirical studies that statistically model environmental effects on population dynamics of several migratory bird species with different life history characteristics and migration strategies. In Chapter II, spruce cone crops are found to have a strong positive effect on the population growth of the great spotted woodpecker (Dendrocopos major), while cone crops of pine another important food resource for the species do not effectively explain population growth. The study compares rate- and ratio-dependent effects of cone availability, using state-space models that distinguish between process and observation error in the time series data. Chapter III shows how drought, in combination with settling behaviour during migration, produces asymmetric spatially synchronous patterns of population dynamics in North American ducks (genus Anas). Chapter IV investigates the dynamics of a Finnish population of skylark (Alauda arvensis), and point out effects of rainfall and habitat quality on population growth. Because the skylark time series and some of the environmental variables included show strong positive autocorrelation, the statistical significances are calculated using a Monte Carlo method, where random autocorrelated time series are generated. Chapter V is a simulation-based study, showing that ignoring observation error in analyses of population time series data can bias the estimated effects and measures of uncertainty, if the environmental variables are autocorrelated. It is concluded that the use of state-space models is an effective way to reach more accurate results. In summary, there are several biological assumptions and methodological issues that can affect the inferential outcome when estimating environmental effects from time series data, and that therefore need special attention. The functional form of the environmental effects and potential interactions between environment and population density are important to deal with. Other issues that should be considered are assumptions about density dependent regulation, modelling potential observation error, and when needed, accounting for spatial and/or temporal autocorrelation.

Molecular dynamics simulations of CXCL-8 and its interactions with a receptor peptide, heparin fragments, and sulfated linked cyclitols

CXCL-8 (Interleukin 8) is a CXC chemokine with a central role in the human immune response. We have undertaken extensive in silico analyses to elucidate the interactions of CXCL-8 with its various binding partners, which are crucial for its biological function. Sequence and structure analyses showed that residues in the thirdq β-sheet and basic residues in the heparin binding site are highly variable, while residues in the second β-sheet are highly conserved. Molecular dynamics simulations in aqueous solution of dimeric CXCL-8 have been performed with starting geometries from both X-ray and NMR structures showed shearing movements between the two antiparallel C-terminal helices. Dynamic conservation analyses of these simulations agreed with experimental data indicating that structural differences between the two structures at quaternary level arise from changes in the secondary structure of the N-terminal loop, the 310-helix, the 30s, 40s, and 50s loops and the third β-sheet, resulting in a different interhelical separation. Nevertheless, the observation of these different states indicates that CXCL-8 has the potential to undergo conformational changes, and it seems likely that this feature is relevant to the mode of binding of glycosaminoglycan (GAG) mimetics such as cyclitols. Simulations of the receptor peptide fragment−CXCL-8 complex identified several specific interactions of the receptor peptide with CXCL-8 that could be exploited in the structure-based design of competitive peptides and nonpeptidic molecules targeting CXCL-8 for combating inflammatory diseases. Simulations of the CXCL-8 dimer complexed with a 24-mer heparin fragment and of the CXCL-8−receptor peptide complex revealed that Arg60, Lys64, and Arg68 in the dimer bind to cyclitols in a horseshoe pattern, defining a region which is spatially distinct from the receptor binding site. There appears to be an optimum number of sulfates and an optimum length of alkyl spacers required for the interaction of cyclitol inhibitors with the dimeric form of CXCL-8. Calculation of the binding affinities of cyclitol inhibitors reflected satisfactorily the ranking of experimentally determined inhibitory potencies. The findings of these molecular modeling studies will help in the search for inhibitors which can modulate various CXCL-8 biological activities and serve as an excellent model system to study CXC-inhibitor interactions.

Surface Proteins of Lactobacillus crispatus: Adhesive Properties and Cell Wall Anchoring

Bacterial surface-associated proteins are important in communication with the environment and bacteria-host interactions. In this thesis work, surface molecules of Lactobacillus crispatus important in host interaction were studied. The L. crispatus strains of the study were known from previous studies to be efficient in adhesion to intestinal tract and ECM. L. crispatus JCM 5810 possess an adhesive surface layer (S-layer) protein, whose functions and domain structure was characterized. We cloned two S-layer protein genes (cbsA; collagen-binding S-layer protein A and silent cbsB) and identified the protein region in CbsA important for adhesion to host tissues, for polymerization into a periodic layer as well as for attachment to the bacterial cell surface. The analysis was done by extensive mutation analysis and by testing His6-tagged fusion proteins from recombinant Escherichia coli as well as by expressing truncated CbsA peptides on the surface of Lactobacillus casei. The N-terminal region (31-274) of CbsA showed efficient and specific binding to collagens, laminin and extracellular matrix on tissue sections of chicken intestine. The N-terminal region also contained the information for formation of periodic S-layer polymer. This region is bordered at both ends by a conserved short region rich in valines, whose substitution to leucines drastically affected the periodic polymer structure. The mutated CbsA proteins that failed to form a periodic polymer, did not bind collagens, which indicates that the polymerized structure of CbsA is needed for collagen-binding ability. The C-terminal region, which is highly identical in S-layer proteins of L. crispatus, Lactobacillus acidophilus and Lactobacillus helveticus, was shown to anchor the protein to the bacterial cell wall. The C-terminal CbsA peptide specifically bound to bacterial teichoic acid and lipoteichoic acids. In conclusion, the N-terminal domain of the S-layer protein of L. crispatus is important for polymerization and adhesion to host tissues, whereas the C-terminal domain anchors the protein to bacterial cell-wall teichoic acids. Lactobacilli are fermentative organisms that effectively lower the surrounding pH. While this study was in progress, plasminogen-binding proteins enolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were identified in the extracellular proteome of L. crispatus ST1. In this work, the cell-wall association of enolase and GAPDH were shown to rely on pH-reversible binding to the cell-wall lipoteichoic acids. Enolase from L. crispatus was functionally compared with enolase from L. johnsonii as well as from pathogenic streptococci (Streptococcus pneumoniae, Streptococcus pyogenes) and Staphylococcus aureus. His6-enolases from commensal lactobacilli bound human plasminogen and enhanced its activation by human plasminogen activators similarly to, or even better than, the enolases from pathogens. Similarly, the His6-enolases from lactobacilli exhibited adhesive characteristics previously assigned to pathogens. The results call for more detailed analyses of the role of the host plasminogen system in bacterial pathogenesis and commensalism as well of the biological role and potential health risk of the extracellular proteome in lactobacilli.

Exposure-related human cancer: Molecular changes in sinonasal cancer and lung cancer, with focus on TP53 mutations

Cancer is a leading cause of death worldwide and the total number of cancer cases continues to increase. Many cancers, for example sinonasal cancer and lung cancer, have clear external risk factors and so are potentially preventable. The occurrence of sinonasal cancer is strongly associated with wood dust exposure and the main risk factor for lung cancer is tobacco smoking. Although the molecular mechanisms involved in lung carcinogenesis have been widely studied, very little is known about the molecular changes leading to sinonasal cancer. In this work, mutations in the tumour suppressor TP53 gene in cases of sinonasal cancer and lung cancer and the associations of these mutations with exposure factors were studied. In addition, another important mechanism in many cancers, inflammation, was explored by analyzing the expression of the inflammation related enzyme, COX-2, in sinonasal cancer. The results demonstrate that TP53 mutations are frequent in sinonasal cancer and lung cancer and in both cancers they are associated with exposure. In sinonasal cancer, the occurrence of TP53 mutation significantly increased in relation to long duration and high level of exposure to wood dust. Smoking was not associated with the overall occurrence of the TP53 mutation in sinonasal cancer, but was associated with multiple TP53 mutations. Furthermore, inflammation appears to play a part in sinonasal carcinogenesis as indicated by our results showing that the expression of COX-2 was associated with adenocarcinoma type of tumours, wood dust exposure and non-smoking. In lung cancer, we detected statistically significant associations between TP53 mutations and duration of smoking, gender and histology. We also found that patients with a tumour carrying a G to T transversion, a mutation commonly found in association with tobacco smoking, had a high level of smoking-related bulky DNA adducts in their non-tumorous lung tissue. Altogether, the information on molecular changes in exposure induced cancers adds to the observations from epidemiological studies and helps to understand the role and impact of different etiological factors, which in turn can be beneficial for risk assessment and prevention.

Using Bayesian networks to model surveillance in complex plant and animal health systems

In this chapter we consider biosecurity surveillance as part of a complex system comprising many different biological, environmental and human factors and their interactions. Modelling and analysis of surveillance strategies should take into account these complexities, and also facilitate the use and integration of the many types of different information that can provide insight into the system as a whole. After a brief discussion of a range of options, we focus on Bayesian networks for representing such complex systems. We summarize the features of Bayesian networks and describe these in the context of surveillance.

Interactions and turnover of the muscular dystrophy protein myotilin

The striated muscle sarcomere is a force generating and transducing unit as well as an important sensor of extracellular cues and a coordinator of cellular signals. The borders of individual sarcomeres are formed by the Z-disks. The Z-disk component myotilin interacts with Z-disk core structural proteins and with regulators of signaling cascades. Missense mutations in the gene encoding myotilin cause dominantly inherited muscle disorders, myotilinopathies, by an unknown mechanism. In this thesis the functions of myotilin were further characterized to clarify the molecular biological basis and the pathogenetic mechanisms of inherited muscle disorders, mainly caused by mutated myotilin. Myotilin has an important function in the assembly and maintenance of the Z-disks probably through its actin-organizing properties. Our results show that the Ig-domains of myotilin are needed for both binding and bundling actin and define the Ig domains as actin-binding modules. The disease-causing mutations appear not to change the interplay between actin and myotilin. Interactions between Z-disk proteins regulate muscle functions and disruption of these interactions results in muscle disorders. Mutations in Z-disk components myotilin, ZASP/Cypher and FATZ-2 (calsarcin-1/myozenin-2) are associated with myopathies. We showed that proteins from the myotilin and FATZ families interact via a novel and unique type of class III PDZ binding motif with the PDZ domains of ZASP and other Enigma family members and that the interactions can be modulated by phosphorylation. The morphological findings typical of myotilinopathies include Z-disk alterations and aggregation of dense filamentous material. The causes and mechanisms of protein aggregation in myotilinopathy patients are unknown, but impaired degradation might explain in part the abnormal protein accumulation. We showed that myotilin is degraded by the calcium-dependent, non-lysosomal cysteine protease calpain and by the proteasome pathway, and that wild type and mutant myotilin differ in their sensitivity to degradation. These studies identify the first functional difference between mutated and wild type myotilin. Furthermore, if degradation of myotilin is disturbed, it accumulates in cells in a manner resembling that seen in myotilinopathy patients. Based on the results, we propose a model where mutant myotilin escapes proteolytic breakdown and forms protein aggregates, leading to disruption of myofibrils and muscular dystrophy. In conclusion, the main results of this study demonstrate that myotilin is a Z-disk structural protein interacting with several Z-disk components. The turnover of myotilin is regulated by calpain and the ubiquitin proteasome system and mutations in myotilin seem to affect the degradation of myotilin, leading to protein accumulations in cells. These findings are important for understanding myotilin-linked muscle diseases and designing treatments for these disorders.

Analysis and Improvements to the Green Falcon Solar Powered UAV

There has recently been a rapidly increasing interest in solar powered UAVs. With the emergence of high power density batteries, long range and low-power micro radio devices, airframes, and powerful micro-processors and motors, small/micro UAVs have become applicable in civilian applications such as remote sensing, mapping, traffic monitoring, search and rescue. The Green Falcon UAV is an innovative project from Queensland University of Technology and has been developed and tested during these past years. It comprises a wide range of subsystems to be analyses and studied such as Solar Panel Cells, Gas sensor, Aerodynamics of the wing and others. Previous test however, resulted in damage to the solar cells and some of the subsystems including motor and ESC. This report describes the repair and verification process followed to improve the efficiency of the Green Falcon UAV. The report shows some of the results obtained in previous static and flight tests as well as some of recommendations.