Genistein and 17β-estradiol fatty acid esters in blood and adipose tissue and the structure-related antioxidant activity of estrogens on lipoproteins

Soy-derived phytoestrogen genistein and 17β-estradiol (E2), the principal endogenous estrogen in women, are also potent antioxidants protecting LDL and HDL lipoproteins against oxidation. This protection is enhanced by esterification with fatty acids, resulting in lipophilic molecules that accumulate in lipoproteins or fatty tissues. The aims were to investigate, whether genistein becomes esterified with fatty acids in human plasma accumulating in lipoproteins, and to develop a method for their quantitation; to study the antioxidant activity of different natural and synthetic estrogens in LDL and HDL; and to determine the E2 esters in visceral and subcutaneous fat in late pregnancy and in pre- and postmenopause. Human plasma was incubated with [3H]genistein and its esters were analyzed from lipoprotein fractions. Time-resolved fluoroimmunoassay (TR-FIA) was used to quantitate genistein esters in monkey plasma after subcutaneous and oral administration. The E2 esters in women s serum and adipose tissue were also quantitated using TR-FIA. The antioxidant activity of estrogen derivatives (n=43) on LDL and HDL was assessed by monitoring the copper induced formation of conjugated dienes. Human plasma was shown to produce lipoprotein-bound genistein fatty acid esters, providing a possible explanation for the previously reported increased oxidation resistance of LDL particles during intake of soybean phytoestrogens. Genistein esters were introduced into blood by subcutaneous administration. The antioxidant effect of estrogens on lipoproteins is highly structure-dependent. LDL and HDL were protected against oxidation by many unesterified, yet lipophilic derivatives. The strongest antioxidants had an unsubstituted A-ring phenolic hydroxyl group with one or two adjacent methoxy groups. E2 ester levels were high during late pregnancy. The median concentration of E2 esters in pregnancy serum was 0.42 nmol/l (n=13) and in pre- (n=8) and postmenopause (n=6) 0.07 and 0.06 nmol/l, respectively. In pregnancy visceral fat the concentration of E2 esters was 4.24 nmol/l and in pre- and postmenopause 0.82 and 0.74 nmol/l. The results from subcutaneous fat were similar. In serum and fat during pregnancy, E2 esters constituted about 0.5 and 10% of the free E2. In non-pregnant women most of the E2 in fat was esterified (the ester/free ratio 150 - 490%). In postmenopause, E2 levels in fat highly exceeded those in serum, the majority being esterified. The pathways for fatty acid esterification of steroid hormones are found in organisms ranging from invertebrates to vertebrates. The evolutionary preservation and relative abundance of E2 esters, especially in fat tissue, suggest a biological function, most likely in providing a readily available source of E2. The body s own estrogen reservoir could be used as a source of E2 by pharmacologically regulating the E2 esterification or hydrolysis.

La coordination et les phrases juxtaposées en français

Coordination and juxtaposed sentences The object of this study is the examination of the relations between juxtaposed clauses in contemporary French. The matter in question is sentences which are composed of several clauses adjoined without a conjunction or other connector, as in: Je détournai les yeux, mon c ur se mit à battre. The aim of the study is to determine, which quality is the relation in these sentences and, on the other hand, what is the part of the coordination there. Furthermore, what is this relation of coordination, which, according to some grammars, manifests through a conjunction of coordination, but which, according to some others is marked in juxtaposed sentences through different features. The study is based on a corpus of written French from literary and journalistic text sources. Syntactic, semantic and textual properties in the clauses are discussed. The analysis points to differences so, it has been noted, in each case, if one of the clauses is affirmative and the other negative and if in the second clause, the subject has not been repeated. Also, an analysis has been made on the ground of the tense, mode, phrase structure type, and thematic structure, taking into account, in each case, if the clauses are identical or different. Punctuation has been one of the properties considered. The final aim has been to eliminate gradually, based on the partition of properties, subordinate sentences, so that only the hard core of coordinate sentences remains. In this way, the coordination could be defined similarly as the phoneme is defined as a group of distinctive features. The quantitative analyses have led to the conclusion that the sentences which, from a semantic point of view, are interpreted as coordinating, contain the least of these differences, while the sentences which can be considered as subordinating present the most of these differences. The conditions of coordination are, in that sense, hierarchical, so that the syntactic constraints have to make room for semantic, textual and cognitive factors. It is interesting to notice that everyone has the ability to produce correct coordinating structures and recognize incorrect coordinating structures. This can be explained by the human ability to categorize which has been widely researched in the semantic of prototype. The study suggests that coordination and subordination could be considered as prototypical cognitive categories based on different linguistic and pragmatic features.

Preliminary Phonological Analysis of Denjongka of Sikkim

This thesis is a preliminary phonological description of the Tibetan-related Denjongka language of Sikkim, India. Because the language has not been much researched and the previous studies have focused on other issues than phonology, the present paper is the first of its kind. The data for this thesis was gathered in Gangtok, the capital of Sikkim, from March to May 2004. I had four language informants from four different locations in Sikkim who spoke different dialects of Denjongka. One of the informants, from whom I recorded c. 900 words and 530 sentences, was used as the main data source for the analysis. First, I will give some ethnographic background information on the people who speak Denjongka. Next, I will discuss first the segmental and then the suprasegmental phonology of the language, which were analysed much in line with American structuralism. I also used acoustic analysis enabled by the Praat-program. Eight vowel phonemes were found. The phonemic status of /E/, however, is still suspect. I present some preliminary evidence for roundedness, frontness and height assimilation among the vowels. In the interpretation adopted in this analysis, there are no diphthongs in Denjongka. Forty consonant phonemes were found: 17 plosives, 7 affricates, 5 fricatives, 5 nasals, 4 liquids and 2 approximants. Denjongka plosives and affricates have four-way aspiration/voicing distinction: voiceless aspirated, voiceless unaspirated, voiceless slightly aspirated (devoiced), and voiced unaspirated. Two voiceless nasals and two voiceless liquids were found. Two phonation types were found to be contrastive, lax/breathy and tense/creaky. Nasalisation and length in vowels are phonemic. Denjongka is an incipient tone language. Tonal phenomena, which involve mainly pitch and phonation type, are complex. Pitch is most of the time predictable from the initial consonant and the phonation type. In some cases, however, pitch is the only contrastive feature between words. The description of Denjongka in this paper differs from the traditional four-tone system, which has been used in many descriptions of Tibetan-related languages. In the four-tone system, pitch is contrastive both in the high and low register, whereas in the present analysis pitch has been established to contrast only in the high register. Lastly, the appendices include a comparative word list of the four Denjongka dialects studied in this thesis.

Strike Hard, Strike Sure - Operation Musketeer : British Military Planning during the Suez Crisis, 1956

This study analyses British military planning and actions during the Suez Crisis in 1956. It seeks to find military reasons for the change of concepts during the planning and compares these reasons with the tactical doctrines of the time. The thesis takes extensive advantage of military documents preserved in the National Archives, London. In order to expand the understanding of the exchange of views during the planning process, the private papers of high ranking military officials have also been consulted. French military documents preserved in the Service Historique de la Defence, Paris, have provided an important point of comparison. The Suez Crisis caught the British armed forces in the middle of a transition phase. The main objective of the armed forces was to establish a credible deterrence against the Soviet Union. However, due to overseas commitments the Middle East playing a paramount role because of its economic importance the armed forces were compelled to also prepare for Limited War and the Cold War. The armed forces were not fully prepared to meet this demand. The Middle Eastern garrison was being re-organised after the withdrawal from the Canal Base and the concept for a strategic reserve was unimplemented. The tactical doctrines of the time were based on experiences from the Second World War. As a result, the British view of amphibious operations and the subsequent campaigns emphasised careful planning, mastery of the sea and the air, sufficient superiority in numbers and firepower, centralised command and extensive administrative preparations. The British military had realized that Nasser could nationalise the Suez Canal and prepared an outline plan to meet this contingency. Although the plan was nothing more than a concept, it was accepted as a basis for further planning when the Canal was nationalised at the end of July. This plan was short-lived. The nominated Task Force Commanders shifted the landing site from Port Said to Alexandria because it enabled faster expansion of the bridgehead. In addition, further operations towards Cairo the hub of Nasser s power would be easier to conduct. The operational concept can be described as being traditional and was in accordance with the amphibious warfare doctrine. This plan was completely changed at the beginning of September. Apparently, General Charles Keightley, the Commander-in-Chief, and the Chairman of the Chiefs of Staff Committee developed the idea of prolonged aerial operations. The essence of the concept was to break the Egyptian will to resist by attacking the oil facilities, the transportation system and the armed forces. This victory through air concept would be supported by carefully planned psychological operations. This concept was in accordance with the Royal Air Force doctrine, which promoted a bomber offensive against selected target categories. General Keightley s plan was accepted despite suspicions at every planning level. The Joint Planning Staff and the Task Force Commanders opposed the concept from the beginning to the end because of its unpredictability. There was no information that suggested the bombing would persuade the Egyptians to submit. This problem was worsened by the fact that British intelligence was unable to provide reliable strategic information. The Task Force Commanders, who were responsible for the tactical plans, were not able to change Keightley s mind, but the concept was expanded to include a traditional amphibious assault on Port Said due to their resistance. The bombing campaign was never tested as the Royal Air Force was denied authorisation to destroy the transportation and oil targets. The Chiefs of Staff and General Keightley were too slow to realise that the execution of the plan depended on the determination of the Prime Minister. However, poor health, a lack of American and domestic support and the indecisiveness of the military had ruined Eden s resolve. In the end, a very traditional amphibious assault, which was bound to succeed at the tactical level but fail at the strategic level, was launched against Port Said.

Changes in Beer Labels and their Meaning : A Holistic Approach to the Semiosic Process

The purpose of this study is to find a framework for a holistic approach to, and form a conceptual toolbox for, investigating changes in signs and in their interpretation. Charles S. Peirce s theory of signs in a communicative perspective is taken as a basis for the framework. The concern directing the study is the problem of a missing framework in analysing signs of visual artefacts from a holistic perspective as well as that of the missing conceptual tools. To discover the possibility of such a holistic approach to semiosic processes and to form a conceptual toolbox the following issues are discussed: i) how the many Objects with two aspects involved in Peirce s definition of sign-action, promote multiple semiosis arising from the same sign by the same Interpretant depending on the domination of the Objects; ii) in which way can the relation of the individual and society or group be made more apparent in the construction of the self since this construction is intertwined with the process of meaning-creation and interpretation; iii) how to account for the fundamental role of emotions in semiosis, and the relation of emotions with the often neglected topic of embodiment; iv) how to take into account the dynamic, mediating and processual nature of sign-action in analysing and understanding the changes in signs and in the interpretation of signs. An interdisciplinary approach is chosen for this dissertation. Concepts that developed within social psychology, developmental psychology, neurosciences and semiotics, are discussed. The common aspect of the approaches is that they in one way or another concentrate on mediation provided by signs in explaining human activity and cognition. The holistic approach and conceptual toolbox found are employed in a case study. This consists of an analysis of beer brands including a comparison of brands from two different cultures. It becomes clear that different theories and approaches have mutual affinities and do complement each other. In addition, the affinities in different disciplines somewhat provide credence to the various views. From the combined approach described, it becomes apparent that by the semiosic process, the emerging semiotic self intertwined with the Umwelt, including emotions, can be described. Seeing the interpretation and meaning-making through semiosis allows for the analysis of groups, taking into account the embodied and emotional component. It is concluded that emotions have a crucial role in all human activity, including so-called reflective thinking, and that emotions and embodiment should be consciously taken into account in analysing signs, the interpretation, and in changes of signs and interpretations from both the social and individual level. The analysis of the beer labels expresses well the intertwined nature of the relationship between signs, individual consumers and society. Many direct influences from society on the label design are found, and also some indirect attitude changes that become apparent from magazines, company reports, etc. In addition, the analysis brings up the issues of the unifying tendency of the visual artefacts of different cultures, but also demonstrates that the visual artefacts are able to hold the local signs and meanings, and sometimes are able to represent the local meanings although the signs have changed in the unifying process.

Intercultural Learning and Hybridity in the Culture Laboratory

The number of immigrant students in vocational education and training is steadily increasing in Finland. This poses challenges for teachers and schools. This research focuses on emerging questions of intercultural learning in the context of immigrant training, and on a method the Culture Laboratory that was developed in an attempt to respond to the challenges. The main methodological and theoretical framework lies in cultural-historical activity theory, developmental work research, and in the concepts of the intercultural and hybridity. The empirical material consists of videotaped recordings of discussions in the Culture Laboratory. The five main research questions focused on the strengths and limitations of the Culture Laboratory as a tool for intercultural learning, the significance of disturbances in it, the potential of suggestions for intercultural learning, paper as a mediating artifact , and the concept of intercultural space. The findings showed that the Culture Laboratory offered a solid background for developing intercultural learning. The disturbances manifested revealed a multitude of scripts and activities. It was also suggested that the structure of expansive learning could start from externalization instead of internalization. The suggestions the participants made opened up a hybrid learning space for intercultural development, and offered a good springboard for new ideas. Learning in Paperland posed both challenges and opportunities for immigrant students, and different paper trails emerged. Intercultural space in the Culture Laboratory was a developmental zone in which a hybrid process of observing, comparing, and creating took place. Key words: intercultural learning, immigrant training, cultural-historical activity theory, developmental work research,

Aivojen jännitevasteiden rekisteröinti useaan äänen piirteeseen yhdellä mittauskerralla terveillä musiikkileikkikoulua käyvillä kaksivuotiailla

The early detection of hearing deficits is important to a child's development. However, examining small children with behavioural methods is often difficult. Research with ERPs (event-related potentials), recorded with EEG (electroencephalography), does not require attention or action from the child. Especially in children's ERP research, it is essential that the duration of a recording session is not too long. A new, faster optimum paradigm has been developed to record MMN (mismatch negativity), where ERPs to several sound features can be recorded in one recording session. This substantially shortens the time required for the experiment. So far, the new paradigm has been used in adult and school-aged children research. This study examines if MMN, LDN (late discriminative negativity) and P3a components can be recorded in two-year-olds with the new paradigm. The standard stimulus (p=0.50) was an 80 dB harmonic tone consisting of three harmonic frequencies (500 Hz, 1000 Hz and 1500 Hz) with a duration of 200 ms. The loudness deviants (p=0.067) were at a level of +6 dB or -6 dB compared to the standards. The frequency deviants (p=0.112) had a fundamental frequency of 550 or 454.4 Hz (small deviation), 625 or 400 Hz (medium deviation) or 750 or 333.3 Hz (large deviation). The duration deviants (p=0.112) had a duration of 175 ms (small deviation), 150 ms (medium deviation) or 100 ms (large deviation). The direction deviants (p=0.067) were presented from the left or right loudspeaker only. The gap deviant (p=0.067) included a 5-ms silent gap in the middle of the sound. Altogether 17 children participated in the experiment, of whom the data of 12 children was used in the analysis. ERP components were observed for all deviant types. The MMN was significant for duration and gap deviants. The LDN was significant for the large duration deviant and all other deviant types. No significant P3a was observed. These results indicate that the optimum paradigm can be used with two-year-olds. With this paradigm, data on several sound features can be recorded in a shorter time than with the previous paradigms used in ERP research.

Mitä autismin kirjon opiskelijat oppivat valmentavassa koulutuksessa

The purpose of this research was to evaluate the special vocational training programme, which aimed at enhancing the pupils with autism spectrum to prepare themselves for work and independent life. The vocational training programme is based on TEACCH (Treatment and Education of Autistic and Related Communication handicapped CHildren), which takes into account the autism spectrum disorders and autistic behaviour. TEACCH is based on the principles of structured teaching, functional teaching and preparation training for work and independent life. The TEACCH has been adapted to Finnish society and the educational system. Treatment programmes were individually designed for each student´s educational needs. There is also an important role for the AAPEP rating scale (Adolescent and Adult Psychoeducational Profile). The AAPEP has been the major tool for planning and following the courses. The AAPEP is an assessment instrument designed by the TEACCH programme, and it is used to provide an evaluation of current and potential skills. The AAPEP contains three scales: a direct observation scale, a home scale and a school / work scale. The AAPEP includes six test variables: vocational skills, independent functions, functional communication, interpersonal behaviour, vocational behaviour and leisure skills; these are evaluated at three levels: pass, emerge and fail. The subjects were 49 students (65% male and 35 % female) with autism spectrum, who have been followed and tested several times, also one year after the vocational training. The design is therefore a longitudinal one. The research data were collected 1997-2004 using the AAPEP rating scales. The teachers have used the AAPEP scales and the codings have been checked by the researcher. The results of the principal component analysis (PCA) suggested that the structure of AAPEP rating scales works quite well as a hypothesis. The factor structure of the scales of the AAPEP was almost the same in these data as in the original publications. The learning-and-changes results showed that learning is a slow process, but that there were also intended changes in several AAPEP areas. The Cohen´s kappa was used as an effect-size measure and the most important result of this research showed that the student´s skills were developing on a school / work scale; vocational skills variable (0,34), vocational behaviour variable (0,28), leisure skills variable (0,26) and on a direct observation scale; interpersonal behaviour variable (0,21). On a home scale skills of some students were developing negatively and also that effect-size was small. The results showed that the students´ vocational skills and vocational behaviour will continue to develop after school in many areas. There were differences between scales. The result of this research shows that the student´s skills were developing significantly in 3 of 48 variables on a direct observation scale and also on a home scale. On a school / work scale student´s skills were developing significantly in 17 of 48 variables. This result implies that students can do the work without extra assistance if there exist continuing supports for the skills after the vocational training. The fully independent life of students will be difficult, because their independent functions, functional communications and leisure skills regressed after the schooling. This seems to indicate that they will not manage their daily life without support. The students and their parents said that the treatment programmes were individually designed for each student s educational needs, and that they were satisfied with the programmes and services. Generally, it can be concluded that vocational special education can be developed for pupils with autistic syndrome and the detailed teaching can be done using TEACCH principles and applying the tool of AAPEP.

Self-Concept and School Achievement of Pupils with Cleft Lip, Cleft Palate or Both : A longitudinal study

The goal of this research was to survey the self-concept and school achievement of pupils with cleft lip, cleft palate or both from juvenile age to adolescence. Longitudinal researches of self-concept and school achievement among pupils with cleft lip, cleft palate or both are uncommon. This research was the first longitudinal research ever conducted in Finland among this population. This research can be considered to be a special educational study because of the target group involved. Self-concept consists of the person s entire personality. Personality is biological and deterministic. Self-concept includes concepts, attitudes and feelings that the person has about him or her qualities, abilities and relations to the environment. The individual associates experiences to this personality with earlier observations through the social interaction. The individual will have the consciousness of the person s existence and action. The target group in this study consisted of Finnish children with clefts, who were comprised of four different age groups. The questionnaire was sent to all subjects (N1 = 419) both times. A total of 74 % of children returned the questionnaire in 1988 (N2=305). 48 % of children returned the questionnaire in 1993 (N3=203). 42% of children returned the questionnaire both times (N4=175) . These 175 children formed the research subjects. The survey was conducted in 1988, and again in 1993. In 1988, the pupils surveyed were 9 to 12 years of age, while in 1993 they were between 14 and 17 years old. The data was collected through the use of a questionnaire, which consisted of common questions and a personality inventory test that was developed for Finnish students by professor Maija-Liisa Rauste-von Wright. Quantitative analysis methods were used to examine the structure of self-concept and school achievement. Structures found in this research were observed in relation to disorder, gender and maturation. According to these results, structures of self-concepts and school achievement are in fact stable. Basic self-concept elements are seen to be formed at an early age. The developmental aspects of self-concept following puberty are observed as the stability of self-concept and as the forming of a general self. The level of school achievement is stable, but the structure of school achievement changes. From these results, it is possible to state that the gender of the child has a statistical significance regarding self-concept and school achievement. However, the experienced disorder does not have statistical significance as regards to self-concept and school achievement. Results of self-concept support the research of self-concept conducted earlier in Finland.

Young, gifted and spiritual -The case of Finnish sixth-grade pupils

The aim of this study was to explore the spirituality of Finnish academically gifted 12 13-year old pre-adolescents (N = 101). Their spirituality was investigated through the following three questions: (1) What is their relationship to religion? (2) How do they perceive transcendence? and (3) How does their search for meaning integrate into their lives? A total of 60 girls and 41 boys participated in the study. They attend a special school, Helsingin Suomalainen yhteiskoulu, in Helsinki, Finland. The school includes classes from grade 3 to upper secondary school and has an entrance test. This study is part of a research project called Actualizing Finnish Giftedness which is funded by the Finnish Academy between 2000 2007 and is led by Professor Tirri. The research project is based on Gardner s Multiple Intelligences theory (Gardner 1993) and on Hay s (1998) work on spirituality. The data in this study was gathered in 2003 and 2004. It includes both qualitative and quantitative material. The emphasis is on data gathered with interviews. The mixed method approach was used as the methodological framework for connecting the qualitative content analysis, phenomenological approach and the quantitative tests of this study. The results of the sub-studies are reported in full in the four original articles. First, the articles show that the pupils connect religion mainly with Christian institutions and do not consider religion and spirituality to overlap. Second, the articles show that the pupils believe in God and the interference of God in their lives and they think that reality includes a spiritual dimension. Third, the pupils had four kinds of existentially significant interests: personal, transcendental, cosmic and ethical. Cosmic interests were especially highlighted in the article concerning boys as nature and science were reported to be integral sources for their existential thinking. In addition, perceptions on God seemed to be connected to the individual s perception on the meaning of life. In RE, spiritual development has been a constant topic of interest since the late eighties. Likewise, recently in gifted education there have been discussions concerning spiritual intelligence (Gardner 1999) and spirituality of the gifted (Kerr & Cohn 2001). Based on the empirical results of the study, this study concludes that education wishing to promote spiritual development should aim at being existentially relevant to the pupils and use their existential search as an integrative framework for their individual talents and skills.

"Haluan tuonne heti!" : Tulevaisuuskuvia ghanalaisten, isobritannialaisten,suomalaisten ja tansanialaisten lasten piirustuksissa

"I want there now!" Images of the future in the drawings of Ghanaian, British, Finnish and Tanzanian children The aim of the Thesis is to examine what kind of images children aged between 8 and 12 years in Ghana, Great Britain, Finland and Tanzania hold of their future. The study is a qualitative analysis based on data that consists of 214 drawings, digitally photographed and analysed using AtlasTI computer program. The data was coded and divided into " families " whose frequencies were compared in order to maintain results. The assignment was given to the children in the language used in the school and it was similar in each country. The children were introduced to the idea with a set of stimulating questions and after that they were asked to draw and colour with a pen a picture of 1) him/herself as an adult, 2) his/her future home and 3) the people and the animals they think they will be living with. The children were also asked to write down the country and the place they believe to live in their future. They were also encouraged to write down e.g. their dream profession, what they would like to have as hobbies in their adulthood and other important things in their lives. The analysis focuses on the content of the drawings instead of artistic or psychological interpretations. The differences between the drawings from different countries as well as the differences in a single country were significant. The current trends and the experiences children had lived through were present in the drawings. There were no differences in the colour of the skin and the most popular professions were doctor, police and football player. The football was very strongly present in all of the data; almost fourth of the children had either drawn or mentioned football as their future profession or hobby. Different flora was present in 84% of Tanzanian and 70% of Ghanaian drawings compared to the 23% of British and 17% of Finnish drawings. Of all the family forms a dream of the traditional nuclear family could be found among 29% of the drawings. Compared to that a total of 30% wanted either a child of their own without a spouse (15%) or a spouse without a child (15%). Also grandparents, childhood friends, other adults, animals or even space aliens were present and sharing a home with the children in the drawings. Of all children 15% wanted to live totally alone in the future. This was most typical (38%) among the Finnish boys. The cat and the dog were the most popular animals to appear in the drawings. Moving abroad proved to be purely a western phenomenon, dreamed by 57% of the British and 18% of the Finnish children. As results, a negative self-image, violence, lack of expressions of positive feelings and solitude among the Finnish boys in the data were very concerning. Keywords: Images of the future, future studies, future-education, picture analysis

Developmental, functional brain imaging and electrophysiological evidence of visual and auditory working memory

Intact function of working memory (WM) is essential for children and adults to cope with every day life. Children with deficits in WM mechanisms have learning difficulties that are often accompanied by behavioral problems. The neural processes subserving WM, and brain structures underlying this system, continue to develop during childhood till adolescence and young adulthood. With functional magnetic resonance imaging (fMRI) it is possible to investigate the organization and development of WM. The present thesis aimed to investigate, using behavioral and neuroimaging methods, whether mnemonic processing of spatial and nonspatial visual information is segregated in the developing and mature human brain. A further aim in this research was to investigate the organization and development of audiospatial and visuospatial information processing in WM. The behavioral results showed that spatial and nonspatial visual WM processing is segregated in the adult brain. The fMRI result in children suggested that memory load related processing of spatial and nonspatial visual information engages common cortical networks, whereas selective attention to either type of stimuli recruits partially segregated areas in the frontal, parietal and occipital cortices. Deactivation mechanisms that are important in the performance of WM tasks in adults are already operational in healthy school-aged children. Electrophysiological evidence suggested segregated mnemonic processing of visual and auditory location information. The results of the development of audiospatial and visuospatial WM demonstrate that WM performance improves with age, suggesting functional maturation of underlying cognitive processes and brain areas. The development of the performance of spatial WM tasks follows a different time course in boys and girls indicating a larger degree of immaturity in the male than female WM systems. Furthermore, the differences in mastering auditory and visual WM tasks may indicate that visual WM reaches functional maturity earlier than the corresponding auditory system. Spatial WM deficits may underlie some learning difficulties and behavioral problems related to impulsivity, difficulties in concentration, and hyperactivity. Alternatively, anxiety or depressive symptoms may affect WM function and the ability to concentrate, being thus the primary cause of poor academic achievement in children.

Zebrafish as a model of Parkinson's disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease among the elderly. Its etiology is unknown and no disease-modifying drugs are available. Thus, more information concerning its pathogenesis is needed. Among other genes, mutated PTEN-induced kinase 1 (PINK1) has been linked to early-onset and sporadic PD, but its mode of action is poorly understood. Most animal models of PD are based on the use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP is metabolized to MPP+ by monoamine oxidase B (MAO B) and causes cell death of dopaminergic neurons in the substantia nigra in mammals. Zebrafish has been a widely used model organism in developmental biology, but is now emerging as a model for human diseases due to its ideal combination of properties. Zebrafish are inexpensive and easy to maintain, develop rapidly, breed in large quantities producing transparent embryos, and are readily manipulated by various methods, particularly genetic ones. In addition, zebrafish are vertebrate animals and results derived from zebrafish may be more applicable to mammals than results from invertebrate genetic models such as Drosophila melanogaster and Caenorhabditis elegans. However, the similarity cannot be taken for granted. The aim of this study was to establish and test a PD model using larval zebrafish. The developing monoaminergic neuronal systems of larval zebrafish were investigated. We identified and classified 17 catecholaminergic and 9 serotonergic neuron populations in the zebrafish brain. A 3-dimensional atlas was created to facilitate future research. Only one gene encoding MAO was found in the zebrafish genome. Zebrafish MAO showed MAO A-type substrate specificity, but non-A-non-B inhibitor specificity. Distribution of MAO in larval and adult zebrafish brains was both diffuse and distinctly cellular. Inhibition of MAO during larval development led to markedly elevated 5-hydroxytryptamine (serotonin, 5-HT) levels, which decreased the locomotion of the fish. MPTP exposure caused a transient loss of cells in specific aminergic cell populations and decreased locomotion. MPTP-induced changes could be rescued by the MAO B inhibitor deprenyl, suggesting a role for MAO in MPTP toxicity. MPP+ affected only one catecholaminergic cell population; thus, the action of MPP+ was more selective than that of MPTP. The zebrafish PINK1 gene was cloned in zebrafish, and morpholino oligonucleotides were used to suppress its expression in larval zebrafish. The functional domains and expression pattern of zebrafish PINK1 resembled those of other vertebrates, suggesting that zebrafish is a feasible model for studying PINK1. Translation inhibition resulted in cell loss of the same catecholaminergic cell populations as MPTP and MPP+. Inactivation of PINK1 sensitized larval zebrafish to subefficacious doses of MPTP, causing a decrease in locomotion and cell loss in one dopaminergic cell population. Zebrafish appears to be a feasible model for studying PD, since its aminergic systems, mode of action of MPTP, and functions of PINK1 resemble those of mammalians. However, the functions of zebrafish MAO differ from the two forms of MAO found in mammals. Future studies using zebrafish PD models should utilize the advantages specific to zebrafish, such as the ability to execute large-scale genetic or drug screens.

Early Childhood Caries and a Community Trial of its Prevention in Tehran, Iran

Varhaislapsuuden karies ja sen ehkäisy kehittyvän terveydenhuollon maassa Varhaislapsuuden karies on merkittävä kansanterveysongelma varsinkin lapsirikkaissa maissa ja väestöissä. Karieksen hoitaminen vie paljon voimavaroja ja aiheuttaa mittavia taloudellisia seuraamuksia. Karies voi ilmaantua lapselle jo vauvaikäisenä, pian ensimmäisten maitohampaiden puhjettua suuhun. Alle 3-vuotiaiden karieksesta on kuitenkin niukasti tilastotietoja. Maailman terveysjärjestökin suosittaa tietojen keräämistä vasta 3-vuotiaiden ikäryhmästä. Heistä kariesta sairastaa Suomessa 16 %, Yhdysvalloissa 25 %, Englannissa 30 %, Iranissa 46 % ja Saudi-Arabiassa 61 %. Tämä väitöstutkimus selvitti karieksen esiintymistä ja sen vaaratekijöitä 1─3-vuotiailla Teheranissa. Lisäksi tutkimus arvioi perusterveydenhuoltoon sisällytetyn karieksen ehkäisyn tuloksellisuutta. Tutkimuskohteiksi arvottiin Teheranista 18 neuvolaa. Jokaisessa oltiin 4 päivää, jolloin kaikkia rokotuksiin tulleita 1─3-vuotiaita äiteineen pyydettiin osallistumaan tutkimukseen. Kahta lukuun ottamatta kaikki äidit suostuivat, ja aineistoon tuli kaikkiaan 504 lasta äiteineen. Kaikki 1-vuotiaat, 242 lasta äiteineen, valittiin karieksen ehkäisykokeiluun. Sitä varten neuvolat jaettiin kolmeen ryhmään, joista kaksi (A ja B) oli koeryhmiä ja yksi (C) oli vertailuryhmä. Tutkimus alkoi äidin haastattelulla. Siinä selvitettiin perheen koulutus- ja tulotaso sekä lapsen ruokinnasta imetyksen kesto, yösyötöt ja päiväaikaan nautitut makeat. Vielä kysyttiin lapsen ja äidin suuhygieniatavoista ja äidin kokemuksista lapsen suun puhdistamisessa. Sitten hammaslääkäri tutki lapsen suun ja kirjasi karieksen ja hammasplakin esiintymät. Suun tutkimuksen jälkeen äiti ja lapsi siirtyivät rokotushuoneeseen. Koeryhmissä (A ja B) äidit saivat terveydenhoitajalta suunterveyttä koskevan esitteen ja kehotuksen lukea se huolellisesti. Lisäksi ryhmässä A terveydenhoitaja kertoi suun ja hampaiden terveydenhoidosta saman esitteen avulla, ja neuvolan henkilökunta muistutti suunhoidon tärkeydestä puhelimitse kahdesti seuraavan puolen vuoden kuluessa. Vertailuryhmässä äideille ei annettu suunhoidon ohjeita. Kaikissa ryhmissä äitejä muistutettiin seuraavan rokotuskerran ajankohdasta, muttei mainittu tulevaa toista hammastarkastusta. Varhaislapsuuden kariesta sairasti ikäryhmästä riippuen 3─26 % tutkituista 1─3-vuotiaista, ja 65─76 %:lla oli hammasplakkia. Äideistä 68 % harjasi hampaansa päivittäin ja 39 % puhdisti lapsensa suun päivittäin. Mitä useammin äiti harjasi omat hampaansa, sitä paremmin hän huolehti lapsen suun puhtaudesta. Rintaruokinta oli yleistä eikä lisännyt kariesvaaraa. Yöllä pullomaitoa saavilla karies oli 5 kertaa yleisempää kuin muilla. Neuvolassa saatu ohjeistus ehkäisi selvästi karieksen syntyä puolen vuoden kokeessa.

Familial aggregation of type 1 diabetes and diabetic nephropathy in Finland

Type 1 diabetes (T1D) is a common, multifactorial disease with strong familial clustering. In Finland, the incidence of T1D among children aged 14 years or under is the highest in the world. The increase in incidence has been approximately 2.4% per year. Although most new T1D cases are sporadic the first-degree relatives are at an increased risk of developing the same disease. This study was designed to examine the familial aggregation of T1D and one of its serious complications, diabetic nephropathy (DN). More specifically the study aimed (1) to determine the concordance rates of T1D in monozygotic (MZ) and dizygotic (DZ) twins and to estimate the relative contributions of genetic and environmental factors to the variability in liability to T1D as well as to study the age at onset of diabetes in twins; (2) to obtain long-term empirical estimates of the risk of T1D among siblings of T1D patients and the factors related to this risk, especially the effect of age at onset of diabetes in the proband and the birth cohort effect; (3) to establish if DN is aggregating in a Finnish population-based cohort of families with multiple cases of T1D, and to assess its magnitude and particularly to find out whether the risk of DN in siblings is varying according to the severity of DN in the proband and/or the age at onset of T1D: (4) to assess the recurrence risk of T1D in the offspring of a Finnish population-based cohort of patients with childhood onset T1D, and to investigate potential sex-related effects in the transmission of T1D from the diabetic parents to their offspring as well as to study whether there is a temporal trend in the incidence. The study population comprised of the Finnish Young Twin Cohort (22,650 twin pairs), a population-based cohort of patients with T1D diagnosed at the age of 17 years or earlier between 1965 and 1979 (n=5,144) and all their siblings (n=10,168) and offspring (n=5,291). A polygenic, multifactorial liability model was fitted to the twin data. Kaplan-Meier analyses were used to provide the cumulative incidence for the development of T1D and DN. Cox s proportional hazards models were fitted to the data. Poisson regression analysis was used to evaluate temporal trends in incidence. Standardized incidence ratios (SIRs) between the first-degree relatives of T1D patients and background population were determined. The twin study showed that the vast majority of affected MZ twin pairs remained discordant. Pairwise concordance for T1D was 27.3% in MZ and 3.8% in DZ twins. The probandwise concordance estimates were 42.9% and 7.4%, respectively. The model with additive genetic and individual environmental effects was the best-fitting liability model to T1D, with 88% of the phenotypic variance due to genetic factors. The second paper showed that the 50-year cumulative incidence of T1D in the siblings of diabetic probands was 6.9%. A young age at diagnosis in the probands considerably increased the risk. If the proband was diagnosed at the age of 0-4, 5-9, 10-14, 15 or more, the corresponding 40-year cumulative risks were 13.2%, 7.8%, 4.7% and 3.4%. The cumulative incidence increased with increasing birth year. However, SIR among children aged 14 years or under was approximately 12 throughout the follow-up. The third paper showed that diabetic siblings of the probands with nephropathy had a 2.3 times higher risk of DN compared with siblings of probands free of nephropathy. The presence of end stage renal disease (ESRD) in the proband increases the risk three-fold for diabetic siblings. Being diagnosed with diabetes during puberty (10-14) or a few years before (5-9) increased the susceptibility for DN in the siblings. The fourth paper revealed that of the offspring of male probands, 7.8% were affected by the age of 20 compared with 5.3% of the offspring of female probands. Offspring of fathers with T1D have 1.7 times greater risk to be affected with T1D than the offspring of mothers with T1D. The excess risk in the offspring of male fathers manifested itself through the higher risk the younger the father was when diagnosed with T1D. Young age at onset of diabetes in fathers increased the risk of T1D greatly in the offspring, but no such pattern was seen in the offspring of diabetic mothers. The SIR among offspring aged 14 years or under remained fairly constant throughout the follow-up, approximately 10. The present study has provided new knowledge on T1D recurrence risk in the first-degree relatives and the risk factors modifying the risk. Twin data demonstrated high genetic liability for T1D and increased heritability. The vast majority of affected MZ twin pairs, however, remain discordant for T1D. This study confirmed the drastic impact of the young age at onset of diabetes in the probands on the increased risk of T1D in the first-degree relatives. The only exception was the absence of this pattern in the offspring of T1D mothers. Both the sibling and the offspring recurrence risk studies revealed dynamic changes in the cumulative incidence of T1D in the first-degree relatives. SIRs among the first-degree relatives of T1D patients seems to remain fairly constant. The study demonstrates that the penetrance of the susceptibility genes for T1D may be low, although strongly influenced by the environmental factors. Presence of familial aggregation of DN was confirmed for the first time in a population-based study. Although the majority of the sibling pairs with T1D were discordant for DN, its presence in one sibling doubles and presence of ESRD triples the risk of DN in the other diabetic sibling. An encouraging observation was that although the proportion of children to be diagnosed with T1D at the age of 4 or under is increasing, they seem to have a decreased risk of DN or at least delayed onset.