8 resultados para Ectodomain Shedding

em Helda - Digital Repository of University of Helsinki


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Rapid change in climate is challenge for the adaptation of forest trees in the future. In wind pollinated tree species pollen mediated long distance gene flow may provide alleles that are (pre)adapted to a future climate. In order to examine the long distance pollen flow in Scots pine (Pinus sylvestris L.), we measured the amount and viability of airborne pollen and flowering phenology in central, northern, and northernmost Finland during four years. Viable airborne pollen grains were detected during female flowering and before local pollen shedding in all study sites. The situation when there was nonlocal pollen in the air lasted from one to four days depending on the year and study site. The amount of nonlocal airborne pollen varied also between years and study sites, the total amount of nonlocal viable pollen in the air was 2.3% from all detected viable pollen grains. The effect of pollen origin on seeds siring ability was studied with artificial pollination experiments. Pollen genotypes originating from southern Finland sired 76% and 48 % of the analysed seeds in competition studies where both pollen origin were introduced simultaneously into the female strobili. We examined the importance of arrival order of pollen grains in to the strobili in a study where pollen genotypes of different origin were introduced in two hours interval. Northern genotypes sired 76% of the analysed seeds when it was injected first, but in the "southern first" experiment both pollen types sired equal amount of seeds. The first pollen grain in the pollen chamber do not always fertilizes the ovum, instead there likely is more complex way of competition between pollen grains. To examine chemically mediated pollen-pollen interactions we conducted in vitro germination experiment where different pollen genotypes had chemical but not physical contact. Both positive and negative effects of interactions were found. We found highly negative effects in germinability of northern pollen grains when they were germinating with southern pollen, and increase in the germinability of southern pollen. There were no variation in the size of the dry pollen grains between pollen origins, and minor variation between different genotypes. After hydration and germination northern pollen grains were larger than southern pollen. Pollen genotypes having high hydration rates had low germinability and tube growth rate, however, germinated pollen grains were larger in size than nongerminated. This supports the suggestion that the early germination and growth of pollen tube is dependent on pollen storage materialsand less dependent on water intake and hydration. Long distance pollen movements and good competition ability of southern pollen makes gene flow possible, although rising temperature and timing of pollen movements may affect pollen competition and the amount of gene flow.

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Our present-day understanding of fundamental constituents of matter and their interactions is based on the Standard Model of particle physics, which relies on quantum gauge field theories. On the other hand, the large scale dynamical behaviour of spacetime is understood via the general theory of relativity of Einstein. The merging of these two complementary aspects of nature, quantum and gravity, is one of the greatest goals of modern fundamental physics, the achievement of which would help us understand the short-distance structure of spacetime, thus shedding light on the events in the singular states of general relativity, such as black holes and the Big Bang, where our current models of nature break down. The formulation of quantum field theories in noncommutative spacetime is an attempt to realize the idea of nonlocality at short distances, which our present understanding of these different aspects of Nature suggests, and consequently to find testable hints of the underlying quantum behaviour of spacetime. The formulation of noncommutative theories encounters various unprecedented problems, which derive from their peculiar inherent nonlocality. Arguably the most serious of these is the so-called UV/IR mixing, which makes the derivation of observable predictions especially hard by causing new tedious divergencies, to which our previous well-developed renormalization methods for quantum field theories do not apply. In the thesis I review the basic mathematical concepts of noncommutative spacetime, different formulations of quantum field theories in the context, and the theoretical understanding of UV/IR mixing. In particular, I put forward new results to be published, which show that also the theory of quantum electrodynamics in noncommutative spacetime defined via Seiberg-Witten map suffers from UV/IR mixing. Finally, I review some of the most promising ways to overcome the problem. The final solution remains a challenge for the future.

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The purpose of the present study was to examine the outcome of pregnancies among HIV-infected women in Helsinki, use of the levonorgestrel-releasing intrauterine system (LNG-IUS) among HIV-infected women and the prevalence and risk factors of cytological and histologically proven cervical lesions in this population. Between 1993 and 2003 a total of 45 HIV-infected women delivered 52 singleton infants. HIV infection was diagnosed during pregnancy in 40% of the mothers. Seventeen of the mothers received antiretroviral (ARV) medication prior to pregnancy and in 34 cases, the medication was started during pregnancy. A good virological response (i.e. HIV RNA load <1000/mL during the last trimester) to ARV medication was achieved in 36/40 (90%) of the patients in whom HI viral load measurements were performed. Of the infants, 92% were born at term, and their mean (±SD) birth weight was 3350±395 g. The Caesarean section rate was low, 25%. All newborns received ARV medication and none of the infants born to mothers with pre-delivery diagnosis of maternal HIV infection were infected. The safety and advantages of the LNG-IUS were studied prospectively (n=12) and retrospectively (n=6). The LNG-IUS was well tolerated and no cases of PID or pregnancy were noted. Menstrual bleeding was reduced significantly during use of the LNG-IUS; this was associated with a slight increase in haemoglobin levels. Serum oestradiol concentrations remained in the follicular range in all subjects. The key finding was that genital shedding of HIV RNA did not change after the insertion of the LNG-IUS. The mean annual prevalence of low-grade squamous intraepithelial lesions (SIL) was 15% and that of high-grade SIL was 5% among 108 systematically followed HIV-infected women during 1989 2003. A reduced CD4 lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection, use of ARV medication and HI viral load were not. The cumulative risk of any type of SIL was 17% after one year and 48% after five years among patients with initially normal Pap smears. The risk of developing SIL was associated with young age and a high initial HI viral load. During the follow-up 51 subjects (n=153) displayed cervical intraepithelial neoplasia (CIN), (16% CIN1 and 18% CIN 2-3). Only one case of cancer of the uterine cervix was detected. Pap smears were reliable in screening for CIN. Both nulliparity (p<0.01) and bacterial vaginosis (p<0.04) emerged as significant risk factors of CIN. In conclusion, a combination of universal antenatal screening and multidisciplinary management allows individualized treatment and prevents vertical transmission of HIV. Use of the LNG-IUS is safe among HIV-infected women and cervicovaginal shedding of HIV RNA is not affected by use of the LNG-IUS. The risk of cervical pre-malignant lesions is high among HIV-infected women despite systematic follow-up.

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The systemic autoinflammatory disorders are a group of rare diseases characterized by periodically recurring episodes of acute inflammation and a rise in serum acute phase proteins, but with no signs of autoimmunity. At present eight hereditary syndromes are categorized as autoinflammatory, although the definition has also occasionally been extended to other inflammatory disorders, such as Crohn s disease. One of the autoinflammatory disorders is the autosomally dominantly inherited tumour necrosis factor receptor-associated periodic syndrome (TRAPS), which is caused by mutations in the gene encoding the tumour necrosis factor type 1 receptor (TNFRSF1A). In patients of Nordic descent, cases of TRAPS and of three other hereditary fevers, hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), chronic infantile neurologic, cutaneous and articular syndrome (CINCA) and familial cold autoinflammatory syndrome (FCAS), have been reported, TRAPS being the most common of the four. Clinical characteristics of TRAPS are recurrent attacks of high spiking fever, associated with inflammation of serosal membranes and joints, myalgia, migratory rash and conjunctivitis or periorbital cellulitis. Systemic AA amyloidosis may occur as a sequel of the systemic inflammation. The aim of this study was to investigate the genetic background of hereditary periodically occurring fever syndromes in Finnish patients, to explore the reliability of determining serum concentrations of soluble TNFRSF1A and metalloproteinase-induced TNFRSF1A shedding as helpful tools in differential diagnostics, as well as to study intracellular NF-κB signalling in an attempt to widen the knowledge of the pathomechanisms underlying TRAPS. Genomic sequencing revealed two novel TNFRSF1A mutations, F112I and C73R, in two Finnish families. F112I was the first TNFRSF1A mutation to be reported in the third extracellular cysteine-rich domain of the gene and C73R was the third novel mutation to be reported in a Finnish family, with only one other TNFRSF1A mutation having been reported in the Nordic countries. We also presented a differential diagnostic problem in a TRAPS patient, emphasizing for the clinician the importance of differential diagnostic vigiliance in dealing with rare hereditary disorders. The underlying genetic disease of the patient both served as a misleading factor, which possibly postponed arrival at the correct diagnosis, but may also have predisposed to the pathologic condition, which led to a critical state of the patient. Using a method of flow cytometric analysis modified for the use on fresh whole blood, we studied intracellular signalling pathways in three Finnish TRAPS families with the F112I, C73R and the previously reported C88Y mutations. Evaluation of TNF-induced phosphorylation of NF-κB and p38, revealed low phosphorylation profiles in nine out of ten TRAPS patients in comparison to healthy control subjects. This study shows that TRAPS is a diagnostic possibility in patients of Nordic descent, with symptoms of periodically recurring fever and inflammation of the serosa and joints. In particular in the case of a family history of febrile episodes, the possibility of TRAPS should be considered, if an etiology of autoimmune or infectious nature is excluded. The discovery of three different mutations in a population as small as the Finnish, reinforces the notion that the extracellular domain of TNFRSF1A is prone to be mutated at the entire stretch of its cysteine-rich domains and not only at a limited number of sites, suggesting the absence of a founder effect in TRAPS. This study also demonstrates the challenges of clinical work in differentiating the symptoms of rare genetic disorders from those of other pathologic conditions and presents the possibility of an autoinflammatory disorder as being the underlying cause of severe clinical complications. Furthermore, functional studies of fresh blood leukocytes show that TRAPS is often associated with a low NF-κB and p38 phosphorylation profile, although low phosphorylation levels are not a requirement for the development of TRAPS. The aberrant signalling would suggest that the hyperinflammatory phenotype of TRAPS is the result of compensatory NF-κB-mediated regulatory mechanisms triggered by a deficiency of the innate immune response.

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Women and Marital Breakdown in South India: Reconstructing Homes, Bonds and Persons is an ethnographic analysis of the situation of divorced and separated women and their families in the South Indian city of Bangalore. The study is based on 16 months of anthropological fieldwork, i.e., participant observation and life history interviews among 50 divorced and separated women from different socio-religious backgrounds in their homes, in the women s organisations and in the Family Court. The study follows the divorced and separated women from their natal homes to their affinal homes through homelessness and legal battles to their reconstructed natal, affinal or single homes in order to find out what it means to be a person within hierarchical gender and kinship relations in South India. Marital breakdown impacts on kin relations and discloses the existing gender relations and power structure through its consequences. It makes the transformability of relational personhood as well as the transformability of relational society and culture visible. Although the study reveals the painful history of women s ill-treatment in marriage, family and kinship systems, it also demonstrates the women s rejection of the domination; and shows their ability to re-negotiate and promote changes not only to their own positions but to the whole hierarchical system as well. The study explores the divorced and separated women s manifold dilemmas, complicated legal battles, and endless arrangements when they have to struggle with the very practical problems of supporting themselves financially, finding and making a new home for themselves, and re-arranging relationships with their kin and friends. As marital breakdown fundamentally transforms the women s relational field, it forces them to recreate substitutive relations in a flexible way and, simultaneously, to re-construct themselves and their lives without a ready or positive cultural or behavioural template. This process reveals the agency of the divorced and separated women as well as shedding light on issues of gender and the cultural construction of the person in South India. This topical study explores the previously neglected subject of marital breakdown in India and shows the new meaning of kinship in South India.

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The reported incidence of human campylobacteriosis in Finland is higher than in most other European countries. A high annual percentage of sporadic infections is of foreign origin, although a notable proportion of summer infections is domestically acquired. While chickens appear to be a major source of campylobacters for humans in most countries, the prevalence of campylobacters is very low in chicken slaughter batches in Finland. Data on other potential animal reservoirs of human pathogenic campylobacters in Finland are scarce. Consequently, this study aimed to investigate the status of Finnish cattle as a potential source of thermophilic Campylobacter spp. and antibiotic-resistant Campylobacter jejuni for human sporadic campylobacter infections of domestic origin. A survey of the prevalence of thermophilic Campylobacter spp. in Finnish cattle studied bovine rectal faecal samples (n=952) and carcass surface samples (n=948) from twelve Finnish slaughterhouses from January to December 2003. The total prevalence of Campylobacter spp. in faecal samples was 31.1%, and in carcass samples 3.5%. Campylobacter jejuni, the most common species, was present in 19.5% of faecal samples and in 3.1% of carcasses. In addition to thermophilic Campylobacter spp., C. hyointestinalis ssp. hyointestinalis was present in bovine samples. The prevalence of campylobacters was higher among beef cattle than among dairy cattle. Using the enrichment method, the number of positive faecal samples was 7.5 times higher than that obtained by direct plating. The predominant serotypes of faecal C. jejuni, determined by serotyping with a set of 25 commercial antisera for heat-stable antigens (Penner), were Pen2 and Pen4-complex, which covered 52% of the samples. Genotyping with pulsed-field gel electrophoresis (PFGE) using SmaI restriction yielded a high diversity of C. jejuni subtypes in cattle. Determining the minimum inhibitory concentrations of ampicillin, enrofloxacin, erythromycin, gentamicin, nalidixic acid, and oxytetracycline among bovine C. jejuni isolates using a commercial broth microdilution method yielded 9% of isolates resistant to at least one of the antimicrobials examined. No multiresistant isolates were found among the bovine C. jejuni strains. The study of the shedding patterns of Campylobacter spp. among three Finnish dairy cattle herds included the examination of fresh faecal samples and tank milk samples taken five times, as well as samples from drinking troughs taken once during the one-year study. The semiquantitative enrichment method detected C. jejuni in 169 of the 340 faecal samples, mostly at low levels. In addition, C. jejuni was present in one drinking trough sample. The prevalence between herds and sampling occasions varied widely. PFGE, using SmaI as restriction enzyme, identified only a few subtypes in each herd. In two 2 of the herds, two subtypes persisted throughout the sampling. Individual animals presented various shedding patterns during the study. Comparison of C. jejuni isolates from humans, chickens and cattle included the design of primers for four new genetic markers selected from completely sequenced C. jejuni genomes 81-176, RM1221 and NCTC 11168, and the PCR examination of domestic human isolates from southern Finland in 1996, 2002 and 2003 (n=309), chicken isolates from 2003, 2006 and 2007 (n=205), and bovine isolates from 2003 (n=131). The results revealed that bovine isolates differed significantly from human and chicken isolates. In particular, the - glutamyl transpeptidase gene was uncommon among bovine isolates. The PFGE genotyping of C. jejuni isolates, using SmaI and KpnI restriction enzymes, included a geographically representative collection of isolates from domestic sporadic human infections, chicken slaughter batches, and cattle faeces and carcasses during the seasonal peak of campylobacteriosis in the summer of 2003. The study determined that 55.4% of human isolates were indistinguishable from those of chickens and cattle. Temporal association between isolates from humans and chickens was possible in 31.4% of human infections. Approximately 19% of the human infections may have been associated with cattle. However, isolates from bovine carcasses and human cases represented different PFGE subtypes. In conclusion, this study suggests that Finnish cattle is a notable reservoir of C. jejuni, the most important Campylobacter sp. in human enteric infections. Although the concentration of these organisms in bovine faeces appeared to be low, excretion can be persistent. The genetic diversity and presence or absence of marker genes support previous suggestions of host-adapted C. jejuni strains, and may indicate variations in virulence between strains from different hosts. In addition to chickens, Finnish cattle appeared to be an important reservoir and possible source of C. jejuni in domestic sporadic human infections. However, sources of campylobacters may differ between rural and urban areas in Finland, and in general, the transmission of C. jejuni of bovine origin probably occurs via other routes than food.

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The neuronal cell adhesion molecule ICAM-5 ICAM-5 (telencephalin) belongs to the intercellular adhesion molecule (ICAM)-subgroup of the immunoglobulin superfamily (IgSF). ICAMs participate in leukocyte adhesion and adhesion-dependent functions in the central nervous system (CNS) through interacting with the leukocyte-specific b2 integrins. ICAM-5 is found in the mammalian forebrain, appears at the time of birth, and is located at the cell soma and neuronal dendrites. Recent studies also show that it is important for the regulation of immune functions in the brain and for the development and maturation of neuronal synapses. The clinical importance of ICAM-5 is still under investigation; it may have a role in the development of Alzheimer s disease (AD). In this study, the role of ICAM-5 in neuronal differentiation and its associations with a-actinin and N-methyl-D-aspartic acid (NMDA) receptors were examined. NMDA receptors (NMDARs) are known to be involved in many neuronal functions, including the passage of information from one neuron to another one, and thus it was thought important to study their role related to ICAM-5. The results suggested that ICAM-5 was able to induce dendritic outgrowth through homophilic adhesion (ICAM-5 monomer binds to another ICAM-5 monomer in the same or neighbouring cell), and the homophilic binding activity appeared to be regulated by monomer/multimer transition. Moreover, ICAM-5 binding to a-actinin was shown to be important for neuritic outgrowth. It was examined whether matrix metalloproteinases (MMPs) are the main enzymes involved in ICAM-5 ectodomain cleavage. The results showed that stimulation of NMDARs leads to MMP activation, cleavage of ICAM-5 and it is accompanied by dendritic spine maturation. These findings also indicated that ICAM-5 and NMDA receptor subunit 1 (NR1) compete for binding to a-actinin, and ICAM-5 may regulate the NR1 association with the actin cytoskeleton. Thus, it is concluded that ICAM-5 is a crucial cell adhesion molecule involved in the development of neuronal synapses, especially in the regulation of dendritic spine development, and its functions may also be involved with memory formation and learning.

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The open development model of software production has been characterized as the future model of knowledge production and distributed work. Open development model refers to publicly available source code ensured by an open source license, and the extensive and varied distributed participation of volunteers enabled by the Internet. Contemporary spokesmen of open source communities and academics view open source development as a new form of volunteer work activity characterized by hacker ethic and bazaar governance . The development of the Linux operating system is perhaps the best know example of such an open source project. It started as an effort by a user-developer and grew quickly into a large project with hundreds of user-developer as contributors. However, in hybrids , in which firms participate in open source projects oriented towards end-users, it seems that most users do not write code. The OpenOffice.org project, initiated by Sun Microsystems, in this study represents such a project. In addition, the Finnish public sector ICT decision-making concerning open source use is studied. The purpose is to explore the assumptions, theories and myths related to the open development model by analysing the discursive construction of the OpenOffice.org community: its developers, users and management. The qualitative study aims at shedding light on the dynamics and challenges of community construction and maintenance, and related power relations in hybrid open source, by asking two main research questions: How is the structure and membership constellation of the community, specifically the relation between developers and users linguistically constructed in hybrid open development? What characterizes Internet-mediated virtual communities and how can they be defined? How do they differ from hierarchical forms of knowledge production on one hand and from traditional volunteer communities on the other? The study utilizes sociological, psychological and anthropological concepts of community for understanding the connection between the real and the imaginary in so-called virtual open source communities. Intermediary methodological and analytical concepts are borrowed from discourse and rhetorical theories. A discursive-rhetorical approach is offered as a methodological toolkit for studying texts and writing in Internet communities. The empirical chapters approach the problem of community and its membership from four complementary points of views. The data comprises mailing list discussion, personal interviews, web page writings, email exchanges, field notes and other historical documents. The four viewpoints are: 1) the community as conceived by volunteers 2) the individual contributor s attachment to the project 3) public sector organizations as users of open source 4) the community as articulated by the community manager. I arrive at four conclusions concerning my empirical studies (1-4) and two general conclusions (5-6). 1) Sun Microsystems and OpenOffice.org Groupware volunteers failed in developing necessary and sufficient open code and open dialogue to ensure collaboration thus splitting the Groupware community into volunteers we and the firm them . 2) Instead of separating intrinsic and extrinsic motivations, I find that volunteers unique patterns of motivations are tied to changing objects and personal histories prior and during participation in the OpenOffice.org Lingucomponent project. Rather than seeing volunteers as a unified community, they can be better understood as independent entrepreneurs in search of a collaborative community . The boundaries between work and hobby are blurred and shifting, thus questioning the usefulness of the concept of volunteer . 3) The public sector ICT discourse portrays a dilemma and tension between the freedom to choose, use and develop one s desktop in the spirit of open source on one hand and the striving for better desktop control and maintenance by IT staff and user advocates, on the other. The link between the global OpenOffice.org community and the local end-user practices are weak and mediated by the problematic IT staff-(end)user relationship. 4) Authoring community can be seen as a new hybrid open source community-type of managerial practice. The ambiguous concept of community is a powerful strategic tool for orienting towards multiple real and imaginary audiences as evidenced in the global membership rhetoric. 5) The changing and contradictory discourses of this study show a change in the conceptual system and developer-user relationship of the open development model. This change is characterized as a movement from hacker ethic and bazaar governance to more professionally and strategically regulated community. 6) Community is simultaneously real and imagined, and can be characterized as a runaway community . Discursive-action can be seen as a specific type of online open source engagement. Hierarchies and structures are created through discursive acts. Key words: Open Source Software, open development model, community, motivation, discourse, rhetoric, developer, user, end-user