Children's physical activity and psychological health: the relevance of intensity

Aim To examine the relevance of physical activity intensity when assessing the relationship between activity and psychological health in 9–10-year-old children. Methods Activity was assessed by accelerometry in 57 boys (n = 23) and girls (n = 34). Total activity and time spent in very light (≤1.9 METs) through to vigorous activity (≥6 METs) were recorded. Psychological health inventories to assess anxiety, depression and aspects of self-worth were completed. Results Time accumulated in very light activity had positive correlations with anxiety and depression (r > 0.30, p < 0.05) and negative correlations with aspects of physical self-worth (r > −0.29, p < 0.05). Time accumulated in vigorous activity had negative correlations with anxiety and behavioural conduct (r > −0.30, p < 0.05) and positive correlation with aspects of physical self-worth (r > 0.28, p < 0.05). Children spending over 4 h in very light intensity activity had more negative psychological profiles than children spending under 4 h at this intensity. Conclusion Aspects of psychological health were negatively correlated with very light intensity activity and positively correlated with vigorous intensity activity. Further research should investigate whether reducing time spent in very light intensity activity and increasing time spent in vigorous intensity activity improves psychological health in children.

Determinants of farmer retirement and farm succession in Finland

In the past decade, the Finnish agricultural sector has undergone rapid structural changes. The number of farms has decreased and the average farm size has increased when the number of farms transferred to new entrants has decreased. Part of the structural change in agriculture is manifested in early retirement programmes. In studying farmers exit behaviour in different countries, institutional differences, incentive programmes and constraints are found to matter. In Finland, farmers early retirement programmes were first introduced in 1974 and, during the last ten years, they have been carried out within the European Union framework for these programmes. The early retirement benefits are farmer specific and de-pend on the level of pension insurance the farmer has paid over his active farming years. In order to predict the future development of the agricultural sector, farmers have been frequently asked about their future plans and their plans for succession. However, the plans the farmers made for succession have been found to be time inconsistent. This study estimates the value of farmers stated succession plans in predicting revealed succession decisions. A stated succession plan exists when a farmer answers in a survey questionnaire that the farm is going to be transferred to a new entrant within a five-year period. The succession is revealed when the farm is transferred to a suc-cessor. Stated and revealed behaviour was estimated as a recursive Binomial Probit Model, which accounts for the censoring of the decision variables and controls for a potential correlation between the two equations. The results suggest that the succession plans, as stated by elderly farmers in the questionnaires, do not provide information that is significant and valuable in predicting true, com-pleted successions. Therefore, farmer exit should be analysed based on observed behaviour rather than on stated plans and intentions. As farm retirement plays a crucial role in determining the characteristics of structural change in agriculture, it is important to establish the factors which determine an exit from farming among eld-erly farmers and how off-farm income and income losses affect their exit choices. In this study, the observed choice of pension scheme by elderly farmers was analysed by a bivariate probit model. Despite some variations in significance and the effects of each factor, the ages of the farmer and spouse, the age and number of potential successors, farm size, income loss when retiring and the location of the farm together with the production line were found to be the most important determi-nants of early retirement and the transfer or closure of farms. Recently, the labour status of the spouse has been found to contribute significantly to individual retirement decisions. In this study, the effect of spousal retirement and economic incentives related to the timing of a farming couple s early retirement decision were analysed with a duration model. The results suggest that an expected pension in particular advances farm transfers. It was found that on farms operated by a couple, both early retirement and farm succession took place more often than on farms operated by a single person. However, the existence of a spouse delayed the timing of early retirement. Farming couples were found to co-ordinate their early retirement decisions when they both exit through agricultural retirement programmes, but such a co-ordination did not exist when one of the spouses retired under other pension schemes. Besides changes in the agricultural structure, the share and amount of off-farm income of a farm family s total income has also increased. In the study, the effect of off-farm income on farmers retirement decisions, in addition to other financial factors, was analysed. The unknown parameters were first estimated by a switching-type multivariate probit model and then by the simulated maxi-mum likelihood (SML) method, controlling for farmer specific fixed effects and serial correlation of the errors. The results suggest that elderly farmers off-farm income is a significant determinant in a farmer s choice to exit and close down the farm. However, off-farm income only has a short term effect on structural changes in agriculture since it does not significantly contribute to the timing of farm successions.

Ecological processes and large-scale climate relationships in northern coniferous forests

Ilmasto vaikuttaa ekologisiin prosesseihin eri tasoilla. Suuren mittakaavan ilmastoprosessit, yhdessä ilmakehän ja valtamerien kanssa, säätelevät paikallisia sääilmiöitä suurilla alueilla (mantereista pallopuoliskoihin). Tämä väistöskirja pyrkii selittämään kuinka suuren mittakaavan ilmasto on vaikuttanut tiettyihin ekologisiin prosesseihin pohjoisella havumetsäalueella. Valitut prosessit olivat puiden vuosilustojen kasvu, metsäpalojen esiintyminen ja vuoristomäntykovakuoriaisen aiheuttamat puukuolemat. Suuren mittakaavan ilmaston löydettiin vaikuttaneen näiden prosessien esiintymistiheyteen, kestoon ja levinneisyyteen keskeisten sään muuttujien välityksellä hyvin laajoilla alueilla. Tutkituilla prosesseilla oli vahva yhteys laajan mittakaavan ilmastoon. Yhteys on kuitenkin ollut hyvin dynaaminen ja muuttunut 1900-luvulla ilmastonmuutoksen aiheuttaessa muutoksia suuren mittakaavan ja alueellisten ilmastoprosessien välisiin sisäisiin suhteisiin.

Biological control of prickly acacia: Current research and future prospects

Prickly acacia, Vachellia nilotica subsp. indica (syn. Acacia nilotica subsp. indica) (Fabaceae), a major weed in the natural grasslands of western Queensland, has been a target of biological control since the 1980s with limited success to date. Surveys in India, based on genetic and climate matching, identified five insects and two rust pathogens as potential agents. Host-specificity tests were conducted for the insects in India and under quarantine conditions in Australia, and for the rust pathogens under quarantine conditions at CABI in the UK. In no-choice tests, the brown leaf-webber, Phycita sp. A, (Lepidoptera: Pyralidae) completed development on 17 non-target plant species. Though the moth showed a clear preference for prickly acacia in oviposition choice trials screening of additional test-plant species was terminated in view of the potential non-target risk. The scale insect Anomalococcus indicus (Hemiptera: Lecanodiaspididae) developed into mature gravid females on 13 out of 58 non-target plant species tested. In the majority of cases very few female scales matured but development was comparable to that on prickly acacia on four of the non-target species. In multiple choice tests, the scale insect showed a significant preference for the target weed over non-target species tested. In a paired-choice trial under field conditions in India, crawler establishment occurred only on prickly acacia and not on the non-target species tested. Further choice trials are to be conducted under natural field conditions in India. A colony of the green leaf-webber Phycita sp. B has been established in quarantine facilities in Australia and host-specificity testing has commenced. The gall-rust Ravenelia acaciae-arabicae and the leaf-rust Ravenelia evansii (Puccineales: Raveneliaceae) both infected and produced viable urediniospores on Vachellia sutherlandii (Fabaceae), a non-target Australian native plant species. Hence, no further testing with the two rust species was pursued. Inoculation trials using the gall mite Aceria liopeltus (Acari: Eriophyidae) from V. nilotica subsp. kraussiana in South Africa resulted in no gall induction on V. nilotica subsp. indica. Future research will focus on the leaf-weevil Dereodus denticollis (Coleoptera: Curculionidae) and the leaf-beetle Pachnephorus sp. (Coleoptera: Chrysomelidae) under quarantine conditions in Australia. Native range surveys for additional potential biological control agents will also be pursued in northern and western Africa.

Living on voles - plastic life of the Ural owl

Individuals face variable environmental conditions during their life. This may be due to migration, dispersion, environmental changes or, for example, annual variation in weather conditions. Genetic adaptation to a novel environment happens through natural selection. Phenotypic plasticity allows, however, a quick individual response to a new environment. Phenotypic plasticity may also be beneficial for individual if the environment is highly variable. For example, eggs are costly to produce. If the food conditions vary significantly between breeding seasons it is useful to be able to adjust the clutch and egg size according to the food abundance. In this thesis I use Ural owl vole system to study phenotypic plasticity and natural selection using a number of reproduction related traits. The Ural owl (Strix uralensis) is a long-lived and sedentary species. The reproduction and survival of the Ural owl, in fact their whole life, is tied to the dramatically fluctuating vole densities. Ural owls do not cause vole cycles but they have to adjust their behaviour to the rather predictable population fluctuations of these small mammals. Earlier work with this system has shown that Ural owl laying date and clutch size are plastic in relation to vole abundance. Further, individual laying date clutch size reaction norms have been shown to vary in the amount of plasticity. My work extends the knowledge of natural selection and phenotypic plasticity in traits related to reproduction. I show that egg size, timing of the onset of incubation and nest defense aggressiveness are plastic traits with fitness consequences for the Ural owl. Although egg size is in general thought to be a fixed characteristic of an individual, this highly heritable trait in the Ural owl is also remarkably plastic in relation to the changes in vole numbers, Ural owls are laying the largest eggs when their prey is most abundant. Timing of the onset of incubation is an individual-specific property and plastic in relation to clutch size. Timing of incubation is an important underlying cause for asynchronous hatching in birds. Asynchronous hatching is beneficial to offspring survival in Ural owl. Hence, timing of the onset of incubation may also be under natural selection. Ural owl females also adjust their nest defense aggressiveness according to the vole dynamics, being most aggressive in years when they produce the largest broods. Individual females show different levels of nest defense aggressiveness. Aggressiveness is positively correlated with the phenotypic plasticity of aggressiveness. As elevated nest defense aggressiveness is selected for, it may promote the plasticity of aggressive nest defense behaviour. All the studied traits are repeatable or heritable on individual level, and their expression is either directly or indirectly sensitive to changes in vole numbers. My work considers a number of important fitness-related traits showing phenotypic plasticity in all of them. Further, in two chapters I show that there is individual variation in the amount of plasticity exhibited. These findings on plasticity in reproduction related traits suggest that variable environments indeed promote plasticity.

Causes and consequences of variation in nestling immune function

Defence against pathogens is a vital need of all living organisms that has led to the evolution of complex immune mechanisms. However, although immunocompetence the ability to resist pathogens and control infection has in recent decades become a focus for research in evolutionary ecology, the variation in immune function observed in natural populations is relatively little understood. This thesis examines sources of this variation (environmental, genetic and maternal effects) during the nestling stage and its fitness consequences in wild populations of passerines: the blue tit (Cyanistes caeruleus) and the collared flycatcher (Ficedula albicollis). A developing organism may face a dilemma as to whether to allocate limited resources to growth or to immune defences. The optimal level of investment in immunity is shaped inherently by specific requirements of the environment. If the probability of contracting infection is low, maintaining high growth rates even at the expense of immune function may be advantageous for nestlings, as body mass is usually a good predictor of post-fledging survival. In experiments with blue tits and haematophagous hen fleas (Ceratophyllus gallinae) using two methods, methionine supplementation (to manipulate nestlings resource allocation to cellular immune function) and food supplementation (to increase resource availability), I confirmed that there is a trade-off between growth and immunity and that the abundance of ectoparasites is an environmental factor affecting allocation of resources to immune function. A cross-fostering experiment also revealed that environmental heterogeneity in terms of abundance of ectoparasites may contribute to maintaining additive genetic variation in immunity and other traits. Animal model analysis of extensive data collected from the population of collared flycatchers on Gotland (Sweden) allowed examination of the narrow-sense heritability of PHA-response the most commonly used index of cellular immunocompetence in avian studies. PHA-response is not heritable in this population, but is subject to a non-heritable origin (presumably maternal) effect. However, experimental manipulation of yolk androgen levels indicates that the mechanism of the maternal effect in PHA-response is not in ovo deposition of androgens. The relationship between PHA-response and recruitment was studied for over 1300 collared flycatcher nestlings. Multivariate selection analysis shows that it is body mass, not PHA-response, that is under direct selection. PHA-response appears to be related to recruitment because of its positive relationship with body mass. These results imply that either PHA-response fails to capture the immune mechanisms that are relevant for defence against pathogens encountered by fledglings or that the selection pressure from parasites is not as strong as commonly assumed.

Gene therapy: Principles, practice, problems and prospects

The remarkable advances made in recombinant DNA technology over the last two decades have paved way for the use of gene transfer to treat human diseases. Several protocols have been developed for the introduction and expression of genes in humans, but the clinical efficacy has not been conclusively demonstrated in any of them. The eventual success of gene therapy for genetic and acquired disorders depends on the development of better gene transfer vectors for sustained, long term expression of foreign genes as well as a better understanding of the pathophysiology of human diseases, it is heartening to note that some of the gene therapy protocols have found other applications such as the genetic immunization or DNA vaccines, which is being heralded as the third vaccine revolution, Gene therapy is yet to become a dream come true, but the light is seen at the end of the tunnel.

Flight metabolic rate in the Glanville fritillary butterfly

Dispersal is a highly important life history trait. In fragmented landscapes the long-term persistence of populations depends on dispersal. Evolution of dispersal is affected by costs and benefits and these may differ between different landscapes. This results in differences in the strength and direction of natural selection on dispersal in fragmented landscapes. Dispersal has been shown to be a nonrandom process that is associated with traits such as flight ability in insects. This thesis examines genetic and physiological traits affecting dispersal in the Glanville fritillary butterfly (Melitaea cinxia). Flight metabolic rate is a repeatable trait representing flight ability. Unlike in many vertebrates, resting metabolic rate cannot be used as a surrogate of maximum metabolic rate as no strong correlation between the two was found in the Glanville fritillary. Resting and flight metabolic rate are affected by environmental variables, most notably temperature. However, only flight metabolic rate has a strong genetic component. Molecular variation in the much-studied candidate locus phosphoglucose isomerase (Pgi), which encodes the glycolytic enzyme PGI, has an effect on carbohydrate metabolism in flight. This effect is temperature dependent: in low to moderate temperatures individuals with the heterozygous genotype at the single nucleotide polymorphism (SNP) AA111 have higher flight metabolic rate than the common homozygous genotype. At high temperatures the situation is reversed. This finding suggests that variation in enzyme properties is indeed translated to organismal performance. High-resolution data on individual female Glanville fritillaries moving freely in the field were recorded using harmonic radar. There was a strong positive correlation between flight metabolic rate and dispersal rate. Flight metabolic rate explained one third of the observed variation in the one-hour movement distance. A fine-scaled analysis of mobility showed that mobility peaked at intermediate ambient temperatures but the two common Pgi genotypes differed in their reaction norms to temperature. As with flight metabolic rate, heterozygotes at SNP AA111 were the most active genotype in low to moderate temperatures. The results show that molecular variation is associated with variation in dispersal rate through the link of flight physiology under the influence of environmental conditions. The evolutionary pressures for dispersal differ between males and females. The effect of flight metabolic rate on dispersal was examined in both sexes in field and laboratory conditions. The relationship between flight metabolic rate and dispersal rate in the field and flight duration in the laboratory were found to differ between the two sexes. In females the relationship was positive, but in males the longest distances and flight durations were recorded for individuals with low flight metabolic rate. These findings may reflect male investment in mate locating. Instead of dispersing, males with high flight metabolic rate may establish territories and follow a perching strategy when locating females and hence move less on the landscape level. Males with low metabolic rate may be forced to disperse due to low competitive success or may show adaptations to an alternative strategy: patrolling. In the light of life history trade-offs and the rate of living theory having high metabolic rate may carry a cost in the form of shortened lifespan. Experiments relating flight metabolic rate to longevity showed a clear correlation in the opposite direction: high flight metabolic rate was associated with long lifespan. This suggests that individuals with high metabolic rate do not pay an extra physiological cost for their high flight capacity, rather there are positive correlations between different measures of fitness. These results highlight the importance of condition.

Effect of soil variability on the bearing capacity of clay and in slope stability problems

Site-specific geotechnical data are always random and variable in space. In the present study, a procedure for quantifying the variability in geotechnical characterization and design parameters is discussed using the site-specific cone tip resistance data (qc) obtained from static cone penetration test (SCPT). The parameters for the spatial variability modeling of geotechnical parameters i.e. (i) existing trend function in the in situ qc data; (ii) second moment statistics i.e. analysis of mean, variance, and auto-correlation structure of the soil strength and stiffness parameters; and (iii) inputs from the spatial correlation analysis, are utilized in the numerical modeling procedures using the finite difference numerical code FLAC 5.0. The influence of consideration of spatially variable soil parameters on the reliability-based geotechnical deign is studied for the two cases i.e. (a) bearing capacity analysis of a shallow foundation resting on a clayey soil, and (b) analysis of stability and deformation pattern of a cohesive-frictional soil slope. The study highlights the procedure for conducting a site-specific study using field test data such as SCPT in geotechnical analysis and demonstrates that a few additional computations involving soil variability provide a better insight into the role of variability in designs.

Ecology, population genetics and conservation of the African violet

The ongoing rapid fragmentation of tropical forests is a major threat to global biodiversity. This is because many of the tropical forests are so-called biodiversity 'hotspots', areas that host exceptional species richness and concentrations of endemic species. Forest fragmentation has negative ecological and genetic consequences for plant survival. Proposed reasons for plant species' loss in forest fragments are, e.g., abiotic edge effects, altered species interactions, increased genetic drift, and inbreeding depression. To be able to conserve plants in forest fragments, the ecological and genetic processes that threaten the species have to be understood. That is possible only after obtaining adequate information on their biology, including taxonomy, life history, reproduction, and spatial and genetic structure of the populations. In this research, I focused on the African violet (genus Saintpaulia), a little-studied conservation flagship from the Eastern Arc Mountains and Coastal Forests hotspot of Tanzania and Kenya. The main objective of the research was to increase understanding of the life history, ecology and population genetics of Saintpaulia that is needed for the design of appropriate conservation measures. A further aim was to provide population-level insights into the difficult taxonomy of Saintpaulia. Ecological field work was conducted in a relatively little fragmented protected forest in the Amani Nature Reserve in the East Usambara Mountains, in northeastern Tanzania, complemented by population genetic laboratory work and ecological experiments in Helsinki, Finland. All components of the research were conducted with Saintpaulia ionantha ssp. grotei, which forms a taxonomically controversial population complex in the study area. My results suggest that Saintpaulia has good reproductive performance in forests with low disturbance levels in the East Usambara Mountains. Another important finding was that seed production depends on sufficient pollinator service. The availability of pollinators should thus be considered in the in situ management of threatened populations. Dynamic population stage structures were observed suggesting that the studied populations are demographically viable. High mortality of seedlings and juveniles was observed during the dry season but this was compensated by ample recruitment of new seedlings after the rainy season. Reduced tree canopy closure and substrate quality are likely to exacerbate seedling and juvenile mortality, and, therefore, forest fragmentation and disturbance are serious threats to the regeneration of Saintpaulia. Restoration of sufficient shade to enhance seedling establishment is an important conservation measure in populations located in disturbed habitats. Long-term demographic monitoring, which enables the forecasting of a population s future, is also recommended in disturbed habitats. High genetic diversities were observed in the populations, which suggest that they possess the variation that is needed for evolutionary responses in a changing environment. Thus, genetic management of the studied populations does not seem necessary as long as the habitats remain favourable for Saintpaulia. The observed high levels of inbreeding in some of the populations, and the reduced fitness of the inbred progeny compared to the outbred progeny, as revealed by the hand-pollination experiment, indicate that inbreeding and inbreeding depression are potential mechanisms contributing to the extinction of Saintpaulia populations. The relatively weak genetic divergence of the three different morphotypes of Saintpaulia ionantha ssp. grotei lend support to the hypothesis that the populations in the Usambara/lowlands region represent a segregating metapopulation (or metapopulations), where subpopulations are adapting to their particular environments. The partial genetic and phenological integrity, and the distinct trailing habit of the morphotype 'grotei' would, however, justify its placement in a taxonomic rank of its own, perhaps in a subspecific rank.

Diabetic ketoacidosis and electroencephalographic changes in newly diagnosed pediatric patients

Objective: To document electroencephalogram (EEG) changes and their correlation with clinical parameters in a newly diagnosed pediatric cohort of type 1 diabetes mellitus (T1DM) patients with and without diabetic ketoacidosis (DKA) and to define their medium term utility and significance. Research design and methods: Prospective longitudinal study of children presenting with T1DM. EEGs were performed within 24 h of diagnosis, day 5, and at 6 months post-diagnosis and reviewed by a neurologist blinded to clinical status. Severity of encephalopathy was graded from 1 to 5 using the Aoki and Lombroso encephalopathy scale. Cognitive abilities were assessed using standardized tests of attention, memory, and intelligence. Results: Eighty eight children were recruited; 34 presented with DKA. Abnormal background slowing was more often observed in the first 24 h in children with DKA (p = 0.01). Encephalopathy scores on day 1 correlated with initial pH, CO2, HCO3, base excess, respiratory rate, heart rate, diastolic blood pressure, and IV fluid intake (all parameters p < 0.05). EEG scores at day 1 did not correlate with contemporaneous mental state or cognition in the medium term. Conclusions: DKA was associated with significant clinical and neurophysiologic signs of brain dysfunction at presentation. While EEG is sensitive to the detection of encephalopathy in newly diagnosed T1DM, it has limited use in identifying children at risk of later cognitive deficits.

Characterization of genomic diversity in extraintestinal pathogenic Escherichia coli (ExPEC) and development of a diagnostic DNA microarray for the differentiation of ExPEC isolates causing urinary tract infections

Extraintestinal pathogenic Escherichia coli (ExPEC) represent a diverse group of strains of E. coli, which infect extraintestinal sites, such as the urinary tract, the bloodstream, the meninges, the peritoneal cavity, and the lungs. Urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC), the major subgroup of ExPEC, are among the most prevalent microbial diseases world wide and a substantial burden for public health care systems. UTIs are responsible for serious morbidity and mortality in the elderly, in young children, and in immune-compromised and hospitalized patients. ExPEC strains are different, both from genetic and clinical perspectives, from commensal E. coli strains belonging to the normal intestinal flora and from intestinal pathogenic E. coli strains causing diarrhea. ExPEC strains are characterized by a broad range of alternate virulence factors, such as adhesins, toxins, and iron accumulation systems. Unlike diarrheagenic E. coli, whose distinctive virulence determinants evoke characteristic diarrheagenic symptoms and signs, ExPEC strains are exceedingly heterogeneous and are known to possess no specific virulence factors or a set of factors, which are obligatory for the infection of a certain extraintestinal site (e. g. the urinary tract). The ExPEC genomes are highly diverse mosaic structures in permanent flux. These strains have obtained a significant amount of DNA (predictably up to 25% of the genomes) through acquisition of foreign DNA from diverse related or non-related donor species by lateral transfer of mobile genetic elements, including pathogenicity islands (PAIs), plasmids, phages, transposons, and insertion elements. The ability of ExPEC strains to cause disease is mainly derived from this horizontally acquired gene pool; the extragenous DNA facilitates rapid adaptation of the pathogen to changing conditions and hence the extent of the spectrum of sites that can be infected. However, neither the amount of unique DNA in different ExPEC strains (or UPEC strains) nor the mechanisms lying behind the observed genomic mobility are known. Due to this extreme heterogeneity of the UPEC and ExPEC populations in general, the routine surveillance of ExPEC is exceedingly difficult. In this project, we presented a novel virulence gene algorithm (VGA) for the estimation of the extraintestinal virulence potential (VP, pathogenicity risk) of clinically relevant ExPECs and fecal E. coli isolates. The VGA was based on a DNA microarray specific for the ExPEC phenotype (ExPEC pathoarray). This array contained 77 DNA probes homologous with known (e.g. adhesion factors, iron accumulation systems, and toxins) and putative (e.g. genes predictably involved in adhesion, iron uptake, or in metabolic functions) ExPEC virulence determinants. In total, 25 of DNA probes homologous with known virulence factors and 36 of DNA probes representing putative extraintestinal virulence determinants were found at significantly higher frequency in virulent ExPEC isolates than in commensal E. coli strains. We showed that the ExPEC pathoarray and the VGA could be readily used for the differentiation of highly virulent ExPECs both from less virulent ExPEC clones and from commensal E. coli strains as well. Implementing the VGA in a group of unknown ExPECs (n=53) and fecal E. coli isolates (n=37), 83% of strains were correctly identified as extraintestinal virulent or commensal E. coli. Conversely, 15% of clinical ExPECs and 19% of fecal E. coli strains failed to raster into their respective pathogenic and non-pathogenic groups. Clinical data and virulence gene profiles of these strains warranted the estimated VPs; UPEC strains with atypically low risk-ratios were largely isolated from patients with certain medical history, including diabetes mellitus or catheterization, or from elderly patients. In addition, fecal E. coli strains with VPs characteristic for ExPEC were shown to represent the diagnostically important fraction of resident strains of the gut flora with a high potential of causing extraintestinal infections. Interestingly, a large fraction of DNA probes associated with the ExPEC phenotype corresponded to novel DNA sequences without any known function in UTIs and thus represented new genetic markers for the extraintestinal virulence. These DNA probes included unknown DNA sequences originating from the genomic subtractions of four clinical ExPEC isolates as well as from five novel cosmid sequences identified in the UPEC strains HE300 and JS299. The characterized cosmid sequences (pJS332, pJS448, pJS666, pJS700, and pJS706) revealed complex modular DNA structures with known and unknown DNA fragments arranged in a puzzle-like manner and integrated into the common E. coli genomic backbone. Furthermore, cosmid pJS332 of the UPEC strain HE300, which carried a chromosomal virulence gene cluster (iroBCDEN) encoding the salmochelin siderophore system, was shown to be part of a transmissible plasmid of Salmonella enterica. Taken together, the results of this project pointed towards the assumptions that first, (i) homologous recombination, even within coding genes, contributes to the observed mosaicism of ExPEC genomes and secondly, (ii) besides en block transfer of large DNA regions (e.g. chromosomal PAIs) also rearrangements of small DNA modules provide a means of genomic plasticity. The data presented in this project supplemented previous whole genome sequencing projects of E. coli and indicated that each E. coli genome displays a unique assemblage of individual mosaic structures, which enable these strains to successfully colonize and infect different anatomical sites.

Transforming growth factor -beta signaling through Smad3 in allergy : Studies in the mechanisms of asthma, atopic dermatitis and allergic contact reactions

Transforming growth factor β signalling through Smad3 in allergy Allergic diseases, such as atopic dermatitis, asthma, and contact dermatitis are complex diseases influenced by both genetic and environmental factors. It is still unclear why allergy and subsequent allergic disease occur in some individuals but not in others. Transforming growth factor (TGF)-β is an important immunomodulatory and fibrogenic factor that regulates cellular processes in injured and inflamed skin. TGF-β has a significant role in the regulation of the allergen-induced immune response participating in the development of allergic and asthmatic inflammation. TGF-β is known to be an immunomodulatory factor in the progression of delayed type hypersensitivity reactions and allergic contact dermatitis. TGF-β is crucial in regulating the cellular responses involved in allergy, such as differentiation, proliferation and migration. TGF-β signals are delivered from the cytoplasm to the nucleus by TGF-β signal transducers called Smads. Smad3 is a major signal transducer in TGF-β -signalling that controls the expression of target genes in the nucleus in a cell-type specific manner. The role of TGF-β-Smad3 -signalling in the immunoregulation and pathophysiology of allergic disorders is still poorly understood. In this thesis, the role of TGF-β-Smad -signalling pathway using Smad3 -deficient knock out mice in the murine models of allergic diseases; atopic dermatitis, asthma and allergic contact reactions, was examined. Smad3-pathway regulates allergen induced skin inflammation and systemic IgE antibody production in a murine model atopic dermatitis. The defect in Smad3 -signalling decreased Th2 cytokine (IL-13 and IL-5) mRNA expression in the lung, modulated allergen induced specific IgG1 response, and affected mucus production in the lung in a murine model of asthma. TGF-β / Smad3 -signalling contributed to inflammatory hypersensitivity reactions and disease progression via modulation of chemokine and cytokine expression and inflammatory cell recruitment, cell proliferation and regulation of the specific antibody response in a murine model of contact hypersensitivity. TGF-β modulates inflammatory responses - at least partly through the Smad3 pathway - but also through other compensatory, non-Smad-dependent pathways. Understanding the effects of the TGF-β signalling pathway in the immune system and in disease models can help in elucidating the multilevel effects of TGF-β. Unravelling the mechanisms of Smad3 may open new possibilities for treating and preventing allergic responses, which may lead to severe illness and loss of work ability. In the future the Smad3 signalling pathway might be a potential target in the therapy of allergic diseases.

Associations of serum perfluoroalkyl acid levels with T-helper cell-specific cytokines in children: By gender and asthma status

Perfluoroalkyl acids (PFAAs) are a group of common chemicals that ubiquitously exist in wildlife and humans. Experimental data suggest that they may alter T-lymphocyte functioning in situ by preferentially enhancing the development of T-helper 2 (TH2)- and inhibiting TH1-lymphocyte development and might increase allergic inflammation, but few human studies have been conducted. To evaluate the association between serum PFAAs concentrations and T-lymphocyte-related immunological markers of asthma in children, and further to assess whether gender modified this association, 231 asthmatic children and 225 non-asthmatic control children from Northern Taiwan were recruited into the Genetic and Biomarker study for Childhood Asthma. Serum concentrations of ten PFAAs and levels of TH1 [interferon (IFN)-γ, interleukin (IL)-2] and TH2 (IL-4 and IL-5) cytokines were measured. The results showed that asthmatics had significantly higher serum PFAAs concentrations compared with the healthy controls. When stratified by gender, a greater number of significant associations between PFAAs and asthma outcomeswere found in males than in females. Among males, adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFAAs exposure ranged from 2.59 (95% CI: 1.14, 5.87) for the perfluorobutanesulfonate (PFBS) to 4.38 (95% CI: 2.02, 9.50) for perfluorooctanesulfonate (PFOS); and serum PFAAs were associated positively with TH2 cytokines and inversely with TH1 cytokines among male asthmatics. Among females, no significant associations between PFAAs and TH2 cytokines could be detected. In conclusion, increased serum PFAAs levels may promote TH cell dysregulation and alter the availability of key TH1 and TH2 cytokines, ultimately contributing to the development of asthma that may differentially impact males to a greater degree than females. These results have potential relevance in asthma prevention.

A study on the variations of optical and physical properties of aerosols over a tropical semi-arid station during grassland fire

The present paper records the results of a case study on the impact of an extensive grassland fire on the physical and optical properties of aerosols at a semi-arid station in southern India for the first time from ground based measurements using a MICROTOPS-II sunphotometer, an aethalometer and a quartz crystal microbalance impactor (QCM). Observations revealed a substantial increase in aerosol optical depth (AOD) at all wavelengths during burning days compared to normal days. High AOD values observed at shorter wavelengths suggest the dominance of accumulation mode particle loading over the study area. Daily mean aerosol size spectra shows, most of the time, power-law distribution. To characterize AOD, the Angstrom parameters (i.e., alpha and beta) were used. Wavelength exponent (1.38) and turbidity coefficient (0.21) are high during burning days compared to normal days, thereby suggesting an increase in accumulation mode particle loading. Aerosol size distribution suggested dominance of accumulation mode particle loading during burning days compared to normal days. A significant positive correlation was observed between AOD at 500 mn and water vapour and negative correlation between AOD at 500 nm and wind speed for burning and non-burning days. Diurnal variations of black carbon (BC) aerosol mass concentrations increased by a factor of similar to 2 in the morning and afternoon hours during burning period compared to normal days.