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Polyglutamine variation in a flowering time protein correlates with island age in a Hawaiian plant radiation
Charlotte Lindqvist, Liisa Laakkonen, Victor A Albert
BMC Evolutionary Biology , 2007, DOI: 10.1186/1471-2148-7-105
Abstract: Here we show that in the Hawaiian mints, extensive polyglutamine (CAG codon repeat) polymorphism within a homolog of the pleiotropic flowering time protein and abscisic acid receptor FCA tracks the natural environmental cline of the island chain, consequent with island age, across a period of 5 million years. CAG expansions, perhaps following their natural tendency to elongate, are more frequent in colonists of recently-formed, nutrient-rich islands than in their forebears on older, nutrient-poor islands. Values for several quantitative morphological variables related to reproductive investment, known from Arabidopsis fca mutant studies, weakly though positively correlate with increasing glutamine tract length. Together with protein modeling of FCA, which indicates that longer polyglutamine tracts could induce suboptimally mobile functional domains, we suggest that CAG expansions may form slightly deleterious alleles (with respect to protein function) that become fixed in founder populations.In the Hawaiian mint FCA system, we infer that contraction of slightly deleterious CAG repeats occurred because of competition for resources along the natural environmental cline of the island chain. The observed geographical structure of FCA variation and its correlation with morphologies expected from Arabidopsis mutant studies may indicate that developmental pleiotropy played a role in the diversification of the mints. This discovery is important in that it concurs with other suggestions that repetitive amino acid motifs might provide a mechanism for driving morphological evolution, and that variation at such motifs might permit rapid tuning to environmental change.The genetic mechanisms underlying organismal radiations are of great interest to biologists. Whereas genetic redundancy, differential regulation of gene transcription, and alternative RNA splicing to produce protein variants have each been implicated as fundamental means by which evolution has tinkered with morphol
Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
Johanna Haiko, Liisa Laakkonen, Benita Westerlund-Wikstr?m, Timo K Korhonen
BMC Evolutionary Biology , 2011, DOI: 10.1186/1471-2148-11-43
Abstract: Pla and Epo expressed in Escherichia coli are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed.We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.Analyses of genomic sequences of bacterial pathogens have given an unprecedented view into their biology and evolutionary processes [1,2]. A conclusion from these studies is that highly similar genes, many of which are associated with bacterial virulence, are found across great phylogenetic distances and in different genetic elements, which is indicative of horizontal gene transfer. These families of virulence factors - including toxins, transport systems, adhesins, and antibiotic resistance factors - have evolved by adaptive radiation of a functional progenitor molecule to and within other strains and species to support survival in differing ecological niches [2]. The adaptation, or "evolutionary fine-tuning" of virulence factors that results in increased fitness, can involve modification of catalytic efficiency or substrate specificity of an enzyme, or alteration of bacterial interactions with target cells [2]. The mechanisms of horizontal gene transfer and th
Two distinct regions in the model protein Peb1 are critical for its heterologous transport out of Escherichia coli
Lena Anton, Katariina Majander, Harri Savilahti, Liisa Laakkonen, Benita Westerlund-Wikstr?m
Microbial Cell Factories , 2010, DOI: 10.1186/1475-2859-9-97
Abstract: When mature Peb1 was expressed without its SecA-YEG -dependent signal sequence and without the putative signal peptidase II recognition sequence in E. coli MKS111ΔHBB lacking the flagellar secretion complex, the protein was found in the periplasm and growth medium which indicated a flagellum-independent translocation. We assessed the Peb1 secretion proficiency by an exhaustive search for transport-affecting regions using a transposition-based scanning mutagenesis strategy. Strikingly, insertion mutagenesis of only two segments, called TAR1 (residues 42 and 43) and TAR2 (residues 173 to 180), prevented Peb1 secretion individually. We confirmed the importance of TAR regions by subsequent site-specific mutagenesis and verified that the secretion deficiency of Peb1 mutants was not due to insolubility or aggregation of the proteins in the cytoplasm. We found by cell fractionation that the mutant proteins were present in the periplasm as well as in the cytoplasm of MKS12. Hence, mutagenesis of TAR regions did not affect export of Peb1 across the cytoplasmic membrane, whereas its export over the outer membrane was markedly impaired.We propose that the localization of the model protein Peb1 in the growth medium of E. coli is due to active secretion by a still unknown pathway of E. coli. The secretion apparently is a two-step process involving a periplasmic step and the TAR regions.Protein secretion is one of the main means by which bacteria interact with their environment. The interaction may take place in a variety of manners: bacteria secrete enzymes, toxins and other virulence factors, excrete metabolic waste products, and export binding proteins into the periplasm for import of nutrients or export of toxic compounds. Bacteria also use different secretion systems to assemble on their surface organelles for motility, adhesion and injection of effector molecules into host cells [1,2]. Bacterial protein secretion systems are of great importance from a virulence-associated v
Psychosocial group intervention to enhance self-management skills of people with dementia and their caregivers: study protocol for a randomized controlled trial
Laakkonen Marja-Liisa,H?ltt? Eeva H,Savikko Niina,Strandberg Timo E
Trials , 2012, DOI: 10.1186/1745-6215-13-133
Abstract: Background After diagnosis of a dementing illness, patients and their spouses have many concerns related to the disease and their future. This often leads to poor psychological well-being and reduced health-related quality of life (HRQoL) of the family. Support for self-management skills has been proven to be an effective method to improve prognosis of asthma, heart failure and osteoarthritis. However, self-management interventions have not been studied in dementia. Therefore, our aim was to examine, in an objective-oriented group intervention, the efficacy of self-management support program (SMP) on the HRQoL of dementia patients and their spousal caregivers as well as on the sense of competence and psychological well-being of caregivers. Methods During the years 2011 to 12, 160 dementia patients and their spouses will be recruited from memory clinics and randomized into two arms: 80 patients for group-based SMP sessions including topics selected by the participants, 80 patients will serve as controls in usual community care. Sessions may include topics on dementia, community services, active lifestyle and prevention for cognitive decline, spousal relationship, future planning and emotional well-being. The patients and spouses will have their separate group sessions (ten participants per group) once a week for eight weeks. Main outcome measures will be patients’ HRQoL (15D) and spousal caregivers’ HRQoL (RAND-36), and sense of competence (SCQ). Secondary measures will be caregivers’ psychological well-being (GHQ-12) and coping resources, patients’ depression, cognition and signs of frailty. Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two-year follow-up. Discussion This is a ‘proof-of-concept’ study to explore the efficacy of group support for self-management skills among dementia families. It will also provide data on cost-effectiveness of the intervention. Trial registration ACTRN12611001173987
Exercise rehabilitation on home-dwelling patients with Alzheimer's disease - a randomized, controlled trial. Study protocol
Kaisu H Pitkala, Minna M Raivio, Marja-Liisa Laakkonen, Reijo S Tilvis, Hannu Kautiainen, Timo E Strandberg
Trials , 2010, DOI: 10.1186/1745-6215-11-92
Abstract: During years 2008-2010, patients with AD (n = 210) living with their spousal caregiver in community are recruited using central AD registers in Finland, and they are offered exercise rehabilitation lasting for one year. The patients are randomized into three arms: 1) tailored home-based exercise twice weekly 2) group-based exercise twice weekly in rehabilitation center 3) control group with usual care and information of exercise and nutrition. Main outcome measures will be Guralnik's mobility and balance tests and FIM-test to assess physical functioning. Secondary measures will be cognition, neuropsychiatric symptoms according to the Neuropsychiatric Inventory, caregivers' burden, depression and health-related quality of life (RAND-36). Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two year follow-up.To our knowledge this is the first large scale trial exploring whether home-dwelling patients with AD will benefit from intense and long-lasting exercise rehabilitation in respect to their mobility and physical functioning. It will also provide data on cost-effectiveness of the intervention.ACTRN12608000037303Dementia is the most important disease group leading to disability and requiring social and health care among older individuals [1]. The most prevalent of dementing illnesses (55-80%) is Alzheimer's disease which leads to gradual and often steady decline of cognitive functioning, to various behavioural and psychological symptoms and physical disability [2]. Disabilities lead to loss of autonomy, require help and support as well as institutional care. Dementia with its consequences is also very expensive for the society [1].One pivotal problem in dementia leading to need for help and institutional care is decline in mobility. Locomotion gets stiff, walking decelerates and falls are common [3]. The stiffness and emerging disabilities makes caregivers' work demanding. Going outdoors, get
Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial
Kaisu H Pitkala, Anna-Liisa Juola, Helena Soini, Marja-Liisa Laakkonen, Hannu Kautiainen, Mariko Teramura-Gronblad, Harriet Finne-Soveri, Mikko Bjorkman
Trials , 2012, DOI: 10.1186/1745-6215-13-85
Abstract: During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately?212) will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months.The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL) according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially hospitalizations.To our knowledge, this is the first large-scale randomized trial exploring whether relatively light intervention, that is, staff training, will have an effect on reducing harmful drugs and improving QOL among institutionalized older people.ACTRN12611001078943
Gender Differences in Dementia Spousal Caregiving
Minna Maria P?ysti,Marja-Liisa Laakkonen,Timo Strandberg,Niina Savikko,Reijo Sakari Tilvis,Ulla Eloniemi-Sulkava,Kaisu Hannele Pitk?l?
International Journal of Alzheimer's Disease , 2012, DOI: 10.1155/2012/162960
Abstract: The proportion of male caregivers is rapidly increasing. However, there are few large scale studies exploring gender differences in the burden or coping with caregiving. We investigated this among caregivers of patients with dementia. The study cohort consisted of 335 dyads of wife-husband couples from two studies including dementia patients and their spousal caregivers. Baseline mini-mental state examination (MMSE), clinical dementia rating scale (CDR), neuropsychiatric inventory (NPI), cornell depression scale and charlson comorbidity index (CCI) were used to describe patients with dementia, Zarit burden scale and geriatric depression scale were used to measure experienced burden and depression of caregivers. Mean age of caregivers was 78 years. There were no differences in depression, satisfaction with life, or loneliness according to caregivers' gender. Male caregivers had more comorbidities than females (CCI 1.9 versus 1.1, ), and the wives of male caregivers had a more severe stage of dementia than husbands of female caregivers (CDR, ; MMSE14.0 versus 17.7, ). However, the mean Zarit burden scale was significantly lower among male than female caregivers (31.5 versus 37.5; ). Lower education of male caregivers tended to be associated with less experienced burden. In conclusion, male caregivers of dementia experienced lower burden than female caregivers despite care recipients' more severe disease. 1. Introduction Alzheimer’s disease and other dementias are the main reasons for need of caregiving at home and for permanent institutional care, and, therefore, they are among the most expensive diseases for our society [1]. Caregivers’ high burden has been examined in a number of studies on dementia [2, 3]. Our society is changing—while caregiving has traditionally been considered as women’s activity [4], the number of male caregivers is rapidly increasing. In fact, men over 65 years in the UK soon outnumber women as caregivers [4, 5]. Women and men may approach their caregiving differently. Whereas men seem to consider it more as a task, women may take it more comprehensively [4, 6, 7]. Coping strategies such as active problem-solving skills are beneficial in caregiving irrespective of caregiver gender [8]. A review of 93 articles on gender differences in caregiving studies [4] reports that most studies conclude that women experience more distress and use more services than men. However, in respect to worrying and stress, studies have had contradictory findings. Furthermore, several studies have reported no gender differences [4, 9]. Ten studies have
Analysis of a Media Channel
Liisa Vesik
Folklore : Electronic Journal of Folklore , 2003,
Abstract: The current paper encompasses a monographic analysis of a media channel, including the organisational structure, spread, usage, the quality of contents and form, and functions of this channel. The channel under discussion is the list sf2001@obs.ee, observed during November 19–25, 2001.
Lemmikloomad Eesti veebis viimasel viiel aastal
Liisa Vesik
M?etagused. Hüperajakiri , 2008,
Abstract: The article outlines the changes that Estonian public pet web pages and pet forums have undergone in 2004–2008. Evolution has caused changes in both the technological solutions of these portals as well as in the contents, reflecting a shift in people’s attitudes and values. Web sites have an important representative role, and the use of ee-domains adds authority on the Estonian web. Recently, there has been a significant shift away from anonymity on message boards in terms of registered and identifyable users as well as a more efficient control of adherence to netiquette. More classifieds are being published online, and not only on free sites. The primary aim of pet forums and portals is dissemination of information, but the sites intended mostly for entertainment purposes are on the rise. Users choose which web environments to visit not only based on their design and ease of use, but based on a combination of these qualities, and also depending on the needs of individual users.
Xenotransplantation and a Potential Threat of Animal Pathogens in Humans
Sihvonen Liisa
Acta Veterinaria Scandinavica , 2004, DOI: 10.1186/1751-0147-45-s1-s35
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