Molecular genetics of Meckel syndrome : Ciliary genes are defective in MKS

Meckel syndrome (MKS, MIM 249000) is a severe developmental disorder that leads to death already in utero or shortly after birth. MKS diagnosis can be established by a careful ultrasound examination already at 11-14 weeks of gestation. The main features of MKS are occipital meningoencephalocele, cystic kidney dysplasia and fibrotic changes of the liver. In addition, polydactyly is frequently reported in the cases. The aim of the study was to characterize the molecular and functional defects in MKS. In this study we were able to identify two major MKS mutations in Finnish population, which cover over 90% of the cases. The first mutation is a 29 bp intronic deletion in the MKS1 gene (c.1483-7_35del) that is found in 70% of the families and the second is a C>T substitution in the coding region of CC2D2A (c.1762C>T), that is found in 20% of the MKS families. Both of these mutations result in abnormal splicing. The discovery of the disease genes has revealed that MKS is caused by primary cilia dysfunction. MKS1 gene has a conserved B9 domain, and it is found in the predicted ciliary proteome. CC2D2A protein is also found in the predicted ciliary proteome and it has a Ca2+ binding domain. The number of genes behind MKS has increased rapidly in the past years and to date, mutations have been identified in five genes (MKS1, TMEM67/MKS3, CEP290/MKS4, RPGRIP1L/MKS5 and CC2D2A/MKS6). Identification of the disease genes mutations has also revealed that MKS is an allelic disorder with other syndromes with overlapping phenotypes. Disorders that are caused by primary cilia dysfunction are collectively known as ciliopathies. Sequence analysis of all the known MKS genes in Finnish and non-Finnish families available to us, where the mutation was still unknown, revealed mutations in 14 out of the 30 families included in the study. When we collected all the reported mutations in MKS genes in different syndromes we could see that there was clearly a genotype-syndrome correlation between the mutations and the syndromes, since the same pair of mutations has never been reported in different syndromes. The basic molecular events behind MKS will not only give us information of this syndrome, but also significant novel information on early fetal development in general.

Sosiaalisen elämän persoonallis-onttinen luonne : Tutkielma Lutherin alkutilaopista

Tämän tutkimuksen tehtävänä oli selvittää, ovatko sosiaaliset järjestykset Martti Lutherin (1483-1546) mukaan Jumalan erityisesti asettamia. Johdannossa luotiin katsaus moderniin Luther-tutkimukseen. Aikaisemmassa tutkimuksessa havaittiin vallitsevan erimielisyyttä siitä, ovatko sosiaaliset järjestykset Jumalan erityisesti asettamia luomisjärjestyksiä (Schöpfungsordnungen), vai ovatko ne Jumalasta vain välillisesti riippuvaisia, järjen vapaasti muutettavissa olevia sosiaalisen elämän muotoja. Lutherin mukaan ihmisen elämälle on luonteenomaista osallisuus kolmesta sosiaalisesta järjestyksestä. Liittyen keskiaikaiseen käsitykseen Luther puhuu kirkon (ecclesia), perheen (oeconomia) ja yhteiskunnan (politia) järjestyksistä, joista kaksi edellistä olivat olemassa jo alkutilassa. Yhteiskunta sai alkunsa vasta syntiinlankeemuksen jälkeen. Tässä tutkimuksessa ihmisen sosiaalisen elämän tarkastelu rajattiin koskemaan alkutilan sosiaalisia järjestyksiä. Tutkimus suoritettiin kaksiosaisesti. Ensimmäisessä pääjaksossa selvitettiin, minkälainen ontologinen luonne ihmisen sosiaalisella elämällä on. Luther ymmärtää teologian tehtävän kaksiosaisesti Jumalan ja ihmisen tuntemiseksi (cognitio Dei et hominis). Teologia ja erityisesti Raamattu sisältävät Lutherin mukaan luonnon kaikkia aspekteja koskevaa tietoa. Tästä syystä immanenttiin todellisuuteen kuuluvien sosiaalisten järjestysten rajaaminen teologisen tiedon ulkopuolelle ei ole perusteltua. Karl Hollin Luther-tulkinnan tavoin tutkimuksessa havaittiin, että ihmisen ja Jumalan suhde perustuu tahdonyhteyteen, josta seuraa ihmisessä Jumalan sana vaikutuksesta syntyvä usko. Tahdonyhteyden johdosta ihminen tulee osalliseksi Jumalan persoonallisista ominaisuuksista siten, että Jumalan mielenliikkeet heijastuvat ihmisen psyykkisiin ominaisuuksiin. Erityisesti tahdon ja järjen alueilla tapahtuvaa partisipaatiota jumalalliseen luontoon voidaan luonnehtia persoonallis-onttiseksi. Persoonallis-onttinen partisipaatio vaikuttaa sekä ihmisen yksilölliseen elämäntodellisuuteen Jumalan kuvana (imago Dei) että yhteisölliseen elämäntodellisuuteen sosiaalisissa järjestyksissä. Toisessa pääjaksossa havaittiin, että kirkko ja perhe ovat Jumalan erityisillä asetussanoilla perustamia sosiaalisia järjestyksiä, joita voidaan kutsua luomisjärjestyksiksi. Sosiaalisina järjestyksinä kirkko ja perhe eivät kuulu Jumalan inhimilliselle järjelle antaman valtuutuksen (mandatum Dei) piiriin. Saman luonteiseen Jumalan käskyyn (mandatum) perustuva kirkko on järjestys (institutio), joka antaa Jumalan sanan voimalla ihmisen "juopuneelle" mielelle muodon (forma). Kirkko ylläpitää ihmisen persoonallis-onttista partisipaatiota sakramentin ja saarnan välityksellä. Jumalanpalveluksesta Jumala puhuttelee ihmistä inhimillisellä kielellä, antaen muodon sekä ihmisen uskolle että immanentit elämänalueet käsittävälle ulkoiselle kuuliaisuudelle. Sosiaaliset normit syntyvät, kun Jumala puhuttelee ihmistä kirkossa. Perheen havaittiin olevan Jumalan asettama sosiaalinen järjestys (institutio), jonka piiriin kuuluvat miehen ja naisen välisen avioliiton lisäksi taloudellinen toiminta ja kasvatus. Avioliitto on luonteeltaan pyhä ja Jumalan käskyyn perustuva. Perhe mahdollistaa ihmisen lisääntymisen, antaen ulkoiselle työlle ja lasten kasvatukselle sosiaalisen struktuurin. Perheen piiriin kuuluva elämä on riippuvainen kirkosta, sillä jumalanpalveluksen ja saarnaviran välittämä Jumalan sana antaa perheessä tapahtuvalle ulkoiselle kuuliaisuudelle muodon. Perhe on riippuvainen persoonallis-onttisesta partisipaatiosta. Tämä ilmenee myös siten, että langenneessa tilassa perhettä koskeva tieto on riippuvainen teologiasta.

Management of bushland vegetation using rainwater harvesting in eastern Kenya.

Microcatchment water harvesting (MCWH) improved the survival and growth of planted trees on heavy soils in eastern Kenya five to six years after planting. In the best method, the cross-tied furrow microcatchments, the mean annual increments (MAI; based on the average biomass of living trees multiplied by tree density and survival) of the total and usable biomass in Prosopis juliflora were 2787 and 1610 kg ha-1 a-1 respectively, when the initial tree density was 500 to 1667 trees per hectare. Based on survival, the indigenous Acacia horrida, A. mellifera and A. zanzibarica were the most suitable species for planting using MCWH. When both survival and yield were considered, a local seed source of the introduced P. juliflora was superior to all other species. The MAI in MCWH was at best distinctly higher than that in the natural vegetation (163­307 and 66­111 kg ha-1 a-1 for total and usable biomass respectively); this cannot satisfy the fuelwood demand of concentrated populations, such as towns or irrigation schemes. The density of seeds of woody species in the topsoil was 40.1 seeds m-2 in the Acacia-Commiphora bushland and 12.6 seeds m-2 in the zone between the bushland and the Tana riverine forest. Rehabilitation of woody vegetation using the soil seed bank alone proved difficult due to the lack of seeds of desirable species. The regeneration and dynamics of woody vegetation were also studied both in cleared and undisturbed bushland. A sub-type of Acacia-Commiphora bushland was identified as Acacia reficiens bushland, in which the dominant Commiphora species is C. campestris. Most of the woody species did not have even-aged populations but cohort structures that were skewed towards young individuals. The woody vegetation and the status of soil nutrients were estimated to recover in 15­20 years on Vertic Natrargid soils after total removal of above-ground vegetation.

Social and material deprivation among youth in Finland : causes, consequences, and coping.

Background: Social and material deprivation is associated with poor health, decreased subjective well-being, and limited opportunities for personal development. To date, little is known about the lived experiences of Finnish low-income youths and the general purpose of this study is to fill this gap. Despite the extensive research on socioeconomic income disparities, only a few scholars have addressed the question of how low socioeconomic position is experienced by disadvantaged people themselves. Little is known about the everyday social processes that lead to decreased well-being of economically and socially disadvantaged citizens. Data: The study is based on the data of 65 autobiographical essays written by Finnish low-income youths aged 14-29 (M=23.51, SD=3.95). The research data were originally collected in a Finnish nationwide writing contest “Arkipäivän kokemuksia köyhyydestä” [Everyday Experiences of Poverty] between June and September of 2006. The contest was partaken by 850 Finnish writers. Methods and key concepts: Autobiographical narratives (N=65) of low-income youths were analyzed based on grounded theory methodology (GTM). The analysis was not built on specific pre-conceived categorizations; it was guided by the paradigm model and so-called “sensitizing concepts”. The concepts this study utilized were based on the research literature on socioeconomic inequalities, resilience, and coping. Socioeconomic inequalities refer to unequal distribution of resources, such as income, social status, and health, between social groups. The concept of resilience refers to an individual’s capacity to cope despite existing risk factors and conditions that are harmful to health and well-being. Coping strategies can be understood as ways by which a person tries to cope with psychological stress in a situation where internal or externals demands exceed one’s resources. The ways to cope are cognitive or behavioral efforts by which individual tries to relieve the stress and gain new resources. Lack of material and social resources is associated with increased exposure to health-related stressors during the life-course. Aims: The first aim of this study is to illustrate how youths with low socioeconomic status perceive the causes and consequences of their social and material deprivation. The second aim is to describe what kind of coping strategies youths employ to cope in their everyday life. The third aim is to build an integrative conceptual framework based on the relationships between causes, consequences, and individual coping strategies associated with deprivation. The analysis was carried out through systematic coding and orderly treatment of the data based on the grounded theory methodology. Results: Finnish low-income youths attributed the primary causes of deprivation to their family background, current socioeconomic status, sudden life changes, and contextual factors. Material and social deprivation was associated with various kinds of negative psychological, social, and material consequences. Youths used a variety of coping strategies that were identified as psychological, social, material, and functional-behavioral. Finally, a conceptual framework was formulated to link the findings together. In the discussion, the results were compared and contrasted to the existing research literature. The main references of the study were: Coping: Aldwin (2007); Lazarus & Folkman (1984); Hobfoll (1989, 2001, 2002). Deprivation: Larivaara, Isola, & Mikkonen (2007); Lister (2004); Townsend (1987); Raphael (2007). Health inequalities: Dahlgren & Whitehead (2007); Lynch. et al. (2000); Marmot & Wilkinson (2006); WHO (2008). Methods: Charmaz (2006); Flick (2009); Strauss & Corbin (1990). Resilience: Cutuli & Masten (2009); Luthar (2006).