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New articles - Uudet artikkelit 12.5.2008 - ISI Web of Knowledge & PubMed Search Alert
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Eight years' experience of molecular identification of human enteroviruses
Blomqvist, S., Paananen, A., Savolainen-Kopra, C., Hovi, T. and Roivainen, M. J Clin Microbiol. 2008. IF 3.445 We have successfully typed 1121 human enterovirus (HEV) isolates during last eight years by adapting partial VP1 sequencing to routine identification of HEV isolated from diverse clinical and environmental specimens. The isolates include 48 of the 59 traditional non-poliovirus HEV serotypes and members of eight newly discovered types, which would have remained untypable by neutralization using the conventional cross-sectional pools of antisera. Davidkin, I., Jokinen, S., Broman, M., Leinikki, P. and Peltola, H. J Infect Dis. 2008; 197(7): 950-6. IF 5.363 BACKGROUND: The persistence of antibodies against measles, mumps, and rubella induced by the measles-mumps-rubella (MMR) vaccine and the kinetics of antibody decline after the second MMR vaccine dose were studied in the same cohort for 20 years. METHODS: Measles, mumps, and rubella antibodies were measured by enzyme immunoassay in 20-year follow-up serum samples (n= 183) of twice-vaccinated individuals, and measles antibodies were also measured in oral fluids (n = 177). Antibody decay was determined in a group (n = 58) with subsequent samples collected 1, 8, and 15 years after the second MMR dose. RESULTS: In total, 95%, 74%, and 100% of 183 vaccinees were still seropositive for measles, mumps, and rubella, respectively, and 85% of 177 vaccinees had measurable measles antibodies in their oral fluids. The antibody levels declined significantly after the second dose, but subsequently the rate of decline was slower. CONCLUSIONS: A high rate of seropositivity was found 20 years after the first MMR dose, particularly for rubella and measles. Our results show that MMR vaccine-induced antibodies wane significantly after the second dose. According to epidemiological data, the protection induced by MMR vaccination in Finland seems to persist at least until early adulthood. However, the situation requires constant vigilance. Fagerlund, R., Melen, K., Cao, X. and Julkunen, I. Cell Signal. 2008. IF 4.887 In resting cells NF-kappaB transcription factors are retained in the cytoplasm as latent inactive complexes, until they are activated and rapidly transported into the nucleus. We show that all NF-kappaB proteins are imported into the nucleus via a subset of importin alpha isoforms. Our data indicate that the NF-kappaB components of the classical and alternative pathways have somewhat different specifities to importin alpha molecules. Based on the results from binding experiments of in vitro-translated and Sendai virus infection-induced or TNF-alpha-stimulated endogenous NF-kappaB proteins, it can be predicted that the specifity of NF-kappaB proteins to importin alpha molecules is different and changes upon the composition of the imported dimer. p52 protein binds directly to importin alpha3, alpha4, alpha5 and alpha6 and c-Rel binds to importin alpha5, alpha6 and alpha7 via a previously described monopartite nuclear localization signals (NLSs). Here we show that RelB, instead, has a bipartite arginine/lysine-rich NLS that mediates the binding of RelB to importin alpha5 and alpha6 and subsequent nuclear translocation of the protein. Moreover, we show that the nuclear import of p52/RelB heterodimers is mediated exclusively by the NLS of RelB. In addition, we found that the NLS of p52 mediates the nuclear import of p52/p65 heterodimers. Haanpera, M., Forssten, S. D., Huovinen, P. and Jalava, J. Antimicrob Agents Chemother. 2008. IF 4.153 In Klebsiella pneumoniae co-occurrence of chromosomal and plasmid-mediated beta-lactamases can hinder their accurate molecular detection. We developed a fast and reliable method allowing typing of isolates carrying more than one SHV gene. The method is based on pyrosequencing the DNA sequence corresponding to the amino acid positions 35 and 238-240. Monitoring success of remediation: Seven case studies of moisture and mold damaged buildings Haverinen-Shaughnessy, U., Hyvarinen, A., Putus, T. and Nevalainen, A. Sci Total Environ. 2008. IF 2.359 Based on seven case studies of buildings that underwent different degrees of moisture and mold damage remediation, we aimed to develop methodology for assessment of the success of the remediation process. Methods used in gauging the success included technical monitoring of performance of building structures and heating, ventilation and air conditioning (HVAC) systems, microbial monitoring of indoor air quality (IAQ), and health effects studies of building occupants. The assessment was based on measurable change in the situations before and after remediation. Based on technical monitoring, remediation was successful in three cases, with partial improvement noted in three cases, whereas no remediation was conducted in one case. Based on microbial monitoring, improvement was detected in one, partial improvement in two and no improvement in two cases, whereas no follow-up was conducted in two cases. Health effect studies (mainly self-reported health status) showed improvement in one case, partial improvement in two cases, and no improvement in two cases, whereas no follow-up was conducted in one case, and in one case, follow-up failed due to low response rate. The results illustrate that it is possible to monitor the effects of remediation using various metrics. However, in some cases, no improvement could be observed in IAQ or occupant health, even if the remediation was considered technically successful, i.e. the remediation was fully completed as recommended. This could be due to many reasons, including: 1) all damage may not have been addressed adequately; 2) IAQ or health may not have been perceived improved regardless of remediation; and/or 3) the methods used may not have been sensitive/specific enough to detect such improvement within the 6-12 months follow-up periods after completion of the remediation. There is a need to further develop tools for monitoring and assessment of the success of moisture damage remediation in buildings. Huttunen, K., Rintala, H., Hirvonen, M. R., Vepsalainen, A., Hyvarinen, A., Meklin, T., Toivola, M. and Nevalainen, A. Environ Res. 2008. IF 2.556 Many building-related health problems coincide with moisture damage and mold growth within a building. Their elimination is assumed to improve indoor air quality. The aim of this study was to follow the success of remediation in two individual buildings by analyzing the microbial flora and immunotoxicological activity of filter samples. We compare results from samples collected from indoor air in the moisture-damaged buildings before and after renovation and results from matched reference buildings and outdoor air. The microbial characteristics of the samples were studied by analyzing ergosterol content and determining the composition of fungal flora with quantitative polymerase chain reaction (QPCR). In addition, the concentrations of particles were monitored with optical particle counter (OPC). The immunotoxicological activity of collected particle samples was tested by exposing mouse macrophages (RAW264.7) for 24h to particle suspension extracted from the filters, and measuring the viability of the exposed cells (MTT-test) and production of inflammatory mediators (nitric oxide, IL-6 and TNFalpha) in cell culture medium by enzyme-linked immunoassay (ELISA). The results show that for Location 1 the renovation decreased the immunotoxicological activity of the particles collected from damaged building, whereas no difference was detected in the corresponding samples collected from the reference building. Interestingly, only slight differences were seen in the concentration of fungi. In the Location 2, a decrease was seen in the concentration of fungi after the renovation, whereas no effect on the immunotoxicological responses was detected. In this case, the immunotoxicological responses to the indoor air samples were almost identical to those caused by the samples from outdoor air. This indicates that the effects of remediation on the indoor air quality may not necessarily be readily measurable either with microbial or toxicological parameters. This may be associated with different spectrum of harmful agents in different mold and moisture-damaged buildings. Jaervinen, T. M., Harjutsalo, V., Kinnunen, L., Miettinen, M. E., Tuomilehto-Wolf, E. and Tuomilehto, J. Genes and Immunity. 2008; 9(3): 207-213. Article. IF 4.533 Children with type 1 diabetes (T1D) susceptibility HLA genotypes are shown to have an increased birthweight. We investigated to what extent T1D-predisposing HLA haplotypes were associated with increased birthweight. A total of 1255 Finnish children comprising those with T1D and their non-diabetic siblings were investigated. A total of 342 children and their non-diabetic parents were HLA genotyped. Birthweight data were obtained from the national Medical Birth Registry. The population-specific diabetogenic haplotype HLA-A2, Cw1, B56, DR4, DQ8 was associated with high birthweight (P=0.0280) in families with a diabetic offspring. Other T1D-predisposing HLA haplotypes showed nonsignificant tendency with high birthweight. More infants with a birthweight >= 4000 g were born in families with a T1D offspring than in the general Finnish population (P=0.0139). The previously observed direct association between birthweight and T1D risk may be mediated through the modulating effects that T1D susceptibility HLA genes have on weight. High birthweight and subsequent weight gain may accelerate the ongoing pancreatic autoimmune process in genetically susceptible individuals. The high proportion of infants having a birthweight >= 4000 g in families with a diabetic offspring raises a concern of potential adverse health outcomes that high birthweight can have. Korhonen, T., Huizink, A. C., Dick, D. M., Pulkkinen, L., Rose, R. J. and Kaprio, J. Drug Alcohol Depend. 2008. IF 3.213 BACKGROUND: Although use of illicit drugs shows varying degree of heritability, the influence of shared and unique environmental factors predominate among adolescents. We explored factors predicting use of cannabis and other illicit drugs among Finnish adolescent twins. METHODS: We used longitudinal data from the FinnTwin12-17 study with baseline at age 11-12 and follow-up at ages 14 and 17(1/2), including 4138 individuals. The outcome was self-reported ever use of cannabis or other illicit drugs at age 17(1/2). The potential predictors were measures reported by the twins, their parents or teachers. As individual factors we tested smoking, alcohol use, behavioral and emotional problems; as peer factors: number of smoking friends and acquaintances with drug experience; as family factors: parental substance use, socio-economic status and pre-natal exposure to nicotine. We used logistic regression models, controlling for twinship, age and sex, to compute odds ratios (OR) for each potential predictor. To adjust for within-family confounds, we conducted conditional logistic regressions among 246 twin pairs discordant for drug use. RESULTS: 13.5% of subjects had initiated use of cannabis or other illicit drugs by age of 17(1/2). When adjusted for within-family confounds, smoking, drinking, and aggressiveness, as well as smoking and drug use among peers predicted use of illicit drugs. In the final regression model, the significant predictors were female sex, early smoking onset, drinking to intoxication, having smoking peers and acquaintances with drug experience, father's weekly drinking to intoxication, and aggressive behavior among boys. Smoking initiation by age of 12 was the most powerful predictor among individuals (OR=26, p<0.001) and within discordant pairs (OR=22, p<0.001). CONCLUSIONS: Early onset smoking is a powerful predictor for subsequent use of illicit drugs among Finnish adolescents, but the causal nature of this relationship needs to be clarified. Association analysis of allelic variants of USF1 in coronary atherosclerosis Kristiansson, K., Ilveskoski, E., Lehtimaki, T., Peltonen, L., Perola, M. and Karhunen, P. J. Arterioscler Thromb Vasc Biol. 2008; 28(5): 983-9. IF 6.883 OBJECTIVE: USF1 regulates the transcription of more than 40 cardiovascular related genes and is well established as a gene associated with familial combined hyperlipidemia, a condition increasing the risk for coronary heart disease. No detailed data, however, exists on the impact of this gene to the critical outcome at the tissue level: different types of atherosclerotic lesions. METHODS AND RESULTS: We analyzed the USF1 in 2 autopsy series of altogether 700 middle-aged men (the Helsinki Sudden Death Study) with quantitative morphometric measurements of coronary atherosclerosis. SNP rs2516839, tagging common USF1 haplotypes, associated with the presence of several types of atherosclerotic lesions, particularly with the proportion of advanced atherosclerotic plaques (P=0.02) and area of calcified lesions (P<0.001) of the coronary arteries. Importantly, carriers of risk alleles of rs2516839 also showed a 2-fold risk for sudden cardiac death (genotype TT versus CC; OR 2.10, 95% CI 1.17 to 3.75, P=0.04). The risk effect of rs2516839 was present also in aorta samples of the men. CONCLUSIONS: Our findings in this unique study sample suggest that USF1 contributes to atherosclerosis, the pathological arterial wall phenotype resulting in coronary heart disease and in its most dramatic consequence-sudden cardiac death. Laaksonen, D. E., Niskanen, L., Mykkanen, H., Juntunen, K. S., Schwab, U., Kolehmainen, M., Rauramaa, R., Tuomilehto, J. and Uusitupa, M. Annals of Medicine. 2008; 40(4): 303-311. Article. IF 4.594 Aim. We assessed the long-term repeatability of the acute insulin response (AIR) and sensitivity index (SI) derived from the frequently sampled intravenous glucose tolerance test (FSIGT). Methods. An FSIGT was performed in 20 women who participated in a 6.5-month rye- and wheat-bread intervention trial, 70 men and women with impaired fasting glycaemia (IFG) or impaired glucose tolerance (IGT) who participated in the Genobin study, and 81 men and women with IGT who participated in the Finnish Diabetes Prevention Study (DPS). Results. The correlation of AIR and S-I at base-line with respective values after the 6.5-8.5-month trials was 0.86-0.88 and 0.71-0.84, and before and after 4 years in the DPS substudy, 0.86 and 0.53. In multivariate analyses, AIR (relative risk for a 1-SD change, 0.67; 95% confidence intervals 0.46-0.97) predicted the conversion from IGT to diabetes in the DPS substudy. Conclusion. AIR is highly repeatable even after 4 years of follow-up. The long-term repeatability of SI is moderate. Our findings emphasize the importance of impaired early insulin secretion in the transition from IGT to diabetes, and the high degree of tracking of measures of early insulin secretion derived from the FSIGT. The epidemiology of severe Streptococcus pyogenes disease in Europe Lamagni, T. L., Darenberg, J., Luca-Harari, B., Siljander, T., Efstratiou, A., Henriques-Normark, B., Vuopio-Varkila, J., Bouvet, A., Creti, R., Ekelund, K., Koliou, M., Reinert, R. R., Stathi, A., Strakova, L., Ungureanu, V., Schalen, C. and Jasir, A. J Clin Microbiol. 2008. IF 3.445 The past two decades have brought worrying increases in severe Streptococcus pyogenes diseases globally. To investigate and compare the epidemiological patterns of these diseases within Europe, data on severe S. pyogenes infections were collected through an EU FP-5 funded programme (Strep-EURO). Prospective population-based surveillance of severe S. pyogenes infection diagnosed during 2003 and 2004 was undertaken in eleven countries across Europe (Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Italy, Romania, Sweden, UK) using a standardised case definition. A total of 5522 cases of severe S. pyogenes infection were identified across the eleven countries during this period. Rates of reported infection varied, reaching 3/100,000 population in the northern European countries. Seasonal patterns of infections showed remarkable congruence between countries. Risk of infection was highest among the elderly, with rates being higher in males than females in most countries. Skin lesions/wounds were the most common predisposing factor, reported in 25% of cases; 21% had no predisposing factors reported. Skin and soft tissue was the most common focus of infection, 32% of patients having cellulitis and 8% necrotizing fasciitis. The overall 7-day case fatality rate was 19%, 44% among cases who developed streptococcal toxic shock syndrome. Findings from Strep-EURO confirm a high incidence of severe S. pyogenes disease in Europe. Furthermore, these results have identified targets for public health intervention, as well as raising awareness of severe S. pyogenes disease across Europe. Penttila, T., Haveri, A., Tammiruusu, A., Vuola, J. M., Lahesmaa, R. and Puolakkainen, M. Microb Pathog. 2008. IF 2.258 In interleukin-10 knock out (IL-10 KO) mice, accelerated clearance of pulmonary Chlamydia pneumoniae infection was observed. On the other hand, the histopathological changes in lung tissue were more pronounced in IL-10 KO mice at all time points after infection and repeated infection than in the wild type mice. Both ex vivo induced antigen-specific proliferation as well as production of proinflammatory cytokines by splenocytes were higher in IL-10 KO mice than in WT mice. Also, intrapulmonary proinflammatory cytokine levels were higher in IL-10 KO mice than in the WT mice. The lack of anti-inflammatory action of IL-10 is likely to contribute to the enhanced clearance but severe inflammation in this experimental model. Pesonen, A. K., Raikkonen, K., Heinonen, K., Kajantie, E., Forsen, T. and Eriksson, J. G. American Journal of Human Biology. 2008; 20(3): 345-351. Article. IF 1.669 Given the ethical limitations of exposing children to experimentally manipulated adverse experiences, evidence of the effects of childhood traumas on subsequent life history are based mostly on women's retrospective reports and animal studies. Only a few prospective studies have assessed the life-long consequences of childhood trauma. We asked whether a traumatic separation from both parents during childhood is associated with reproductive and marital traits later in life, measured by age of onset of menarche, timing of menopause, period of fertile years, age at first childbirth, birth spacing, number of children, and history of divorce. We studied members of the 1934-1944 Helsinki Birth Cohort, including 396 former war evacuees from varying socioeconomic backgrounds, who were sent unaccompanied by their parents to temporary foster families in Sweden and Denmark, and 503 participants who had no separation experiences. Data on separation experiences, number of children, and divorces experienced came from national registers, and the remaining data from a survey among the participants aged 61.6 years (SD = 2.9). Former evacuees had earlier menarche, earlier first childbirth (men), more children by late adulthood (women), and shorter interbirth intervals (men), than the non-separated. A traumatic experience in childhood is associated with significant alterations in reproductive and marital traits, which characterize both women and men. The implications are relevant to the 9.2 million child refugees living throughout the world today. Genetic regulation of growth from birth to 18 years of age: The Swedish young male twins study Silventoinen, K., Pietilainen, K. H., Tynelius, P., Sorensen, T. I. A., Kaprio, J. and Rasmussen, F. American Journal of Human Biology. 2008; 20(3): 292-298. Article. IF 1.669 Growth is a complex process, and only little is known on the genetic regulation of it. We analyzed the effect of genetic and environmental factors on growth in a longitudinal Swedish cohort of 231 monozygotic and 144 dizygotic twin pairs born 1973-1979 with length or height measured annually from birth to age 18. The data were analyzed by two different multivariate variance component models for twin data using the Mx statistical package. At birth and 1 year of age, a substantial part of the variation in length was because of common environment (50 and 57%, respectively) and the effect of genetic factors was minor. After 2 years of age, 91-97% of the variation of height could be explained by genetic differences whereas the rest was because of environmental variation not shared by twins. The genetic correlation between heights at ages 2 and 18 was 0.73 (95% confidence intervals 0.68-0.77) showing that 53% of the genes affecting height at these ages are the same or closely linked; with increasing age the correlation with genetic effects at age 18 become subsequently stronger. Especially in mid-childhood, growth was largely regulated by the same genetic 14 factors. During puberty new genetic factors started to affect height, but also genetic variation affecting height at previous ages remained. These results suggest that genetic regulation of growth is rather uniform, which is encouraging for further efforts to identify genes affecting growth. Binding of LL-37 to model biomembranes: Insight into target vs host cell recognition Sood, R., Domanov, Y., Pietiainen, M., Kontinen, V. P. and Kinnunen, P. K. J. Biochimica Et Biophysica Acta-Biomembranes. 2008; 1778(4): 983-996. Article. IF 3.587 Pursuing the molecular mechanisms of the concentration dependent cytotoxic and hemolytic effects of the human antimicrobial peptide LL-37 on cells, we investigated the interactions of this peptide with lipids using different model membranes, together with fluorescence spectroscopy for the Trp-containing mutant LL-37(F27W). Minimum concentrations inhibiting bacterial growth and lipid interactions assessed by dynamic light scattering and monolayer penetration revealed the mutant to retain the characteristics of native LL-37. Although both LL-37 and the mutant intercalated effectively into zwitterionic phowsphatidylcholine membranes the presence of acidic phospholipids caused augmented membrane binding. Interestingly, strongly attenuated intercalation of LL-37 into membranes containing both cholesterol and sphingomyelin (both at X=0.3) was observed. Accordingly, the distinction between target and host cells by LL-37 is likely to derive from i) acidic phospholipids causing enhanced association with the former cells as well as ii) from attenuated interactions with the outer surface of the plasma membrane of the peptide secreting host, imposed by its high content of cholesterol and sphingomyelin. Our results further suggest that LL-37 may exert its antimicrobial effects by compromising the membrane barrier properties of the target microbes by a mechanism involving cytotoxic oligomers, similarly to other peptides forming amyloid-like fibers in the presence of acidic phospholipids. (c) 2007 Elsevier B.V. All rights reserved. Association of a Nonsynonymous Variant of DAOA with Visuospatial Ability in a Bipolar Family Sample Soronen, P., Silander, K., Antila, M., Palo, O. M., Tuulio-Henriksson, A., Kieseppa, T., Ellonen, P., Wedenoja, J., Turunen, J. A., Pietilainen, O. P., Hennah, W., Lonnqvist, J., Peltonen, L., Partonen, T. and Paunio, T. Biol Psychiatry. 2008. IF 7.154 BACKGROUND: Bipolar disorder and schizophrenia are hypothesized to share some genetic background. METHODS: In a two-phase study, we evaluated the effect of five promising candidate genes for psychotic disorders, DAOA, COMT, DTNBP1, NRG1, and AKT1, on bipolar spectrum disorder, psychotic disorder, and related cognitive endophenotypes in a Finnish family-based sample ascertained for bipolar disorder. RESULTS: In initial screening of 362 individuals from 63 families, we found only marginal evidence for association with the diagnosis-based dichotomous classification. Those associations did not strengthen when we genotyped the complete sample of 723 individuals from 180 families. We observed a significant association of DAOA variants rs3916966 and rs2391191 with visuospatial ability (Quantitative Transmission Disequilibrium Test [QTDT]; p = 4 x 10(-6) and 5 x 10(-6), respectively) (n = 159) with the two variants in almost complete linkage disequilibrium. The COMT variant rs165599 also associated with visuospatial ability, and in our dataset, we saw an additive effect of DAOA and COMT variants on this neuropsychological trait. CONCLUSIONS: The ancestral allele (Arg) of the nonsynonymous common DAOA variant rs2391191 (Arg30Lys) was found to predispose to impaired performance. The DAOA gene may play a role in predisposing individuals to a mixed phenotype of psychosis and mania and to impairments in related neuropsychological traits. Tuokkola, J., Kaila, M., Pietinen, P., Simell, O., Knip, M. and Virtanen, S. M. J Eval Clin Pract. 2008. IF 1.263 Rationale, aims and objectives A third of parents suspect food allergy in their children. Questionnaire-based studies usually overestimate the occurrence of food allergies. The aim of the present study was to validate a study questionnaire by comparing children's use of special diets as reported by parents with patient records at the hospital. Methods A population-based cohort with genetic susceptibility to type 1 diabetes (15% of those screened) was recruited in the Tampere area between 1997 and 2001, and followed for development of food allergy for 3 years. Food allergies and other special diets were queried at the age of 3 years with a structured questionnaire. The hospital records of the children, whose parents had reported an elimination diet of the child, were studied to validate the parental reports of food allergies. The hospital database was also checked for the respective diagnosis codes to estimate underreporting. Results Altogether, 1122 parents returned the questionnaire at the study center visit when the child was 3 years old. Food allergy was reported by 15.0% of the parents. In 10.6% of the children food allergy had been diagnosed or confirmed at the hospital. Hospital-confirmed food allergy was unreported in 0.9% of the cases. The measure of agreement between reported and hospital-confirmed food allergies, using crosstabulation with Cohen's Kappa, was within 0.71-0.88 for cow's milk allergy, 0.74-0.82 for cereal allergy and 0.66-0.86 for any reported food allergy. Conclusion We found that the validity of the questionnaire obtaining information on food allergies of infants and young children was good to excellent based on a comparison between parental reports and information obtained from patient records. Tuomilehto, H., Peltonen, M., Partinen, M., Seppa, J., Saaristo, T., Korpi-Hyovalti, E., Oksa, H., Puolijoki, H., Saltevo, J., Vanhala, M. and Tuomilehto, J. Sleep Medicine. 2008; 9(3): 221-227. Article. IF 2.926 Objective: To examine the association between sleep duration with type 2 diabetes and abnormal glucose tolerance among middle-aged men and women in Finland. Methods: The FIN-D2D survey is a population-based cross-sectional multicentre study in Finland, with 1336 men and 1434 women aged 45-74 participating in the survey during 2004 and 2005. A health examination including ail oral glucose tolerance test and sleep questionnaire was performed for all participants. Results: There was an independent association between abnormal sleeping times and type 2 diabetes in middle-aged women. Even after adjustments for age, body mass index, sleep apnea probability, smoking, physical activity, and central nervous system-affect in g medication, sleep duration of 6 h or less or 8 h or longer was independently associated with type 2 diabetes. There was no increase in the prevalence of diabetes in middle-aged men with abnormal sleeping times. Conclusion: Short (<= 6 h) or long (>= 8 h) sleep duration is related to an increased risk of type 2 diabetes in middle-aged women but not in men. (C) 2007 Elsevier B.V. All rights reserved. Cortical gray matter density in twins discordant for bipolar I disorder Van Erp, T. G. M., Kieseppa, T., Bearden, C. E., Sun, D., Zimmerman, L. L., Tran, H. L., Correll, C., Wobbekind, A., Haukka, J., Partonen, T., Huttunen, M. O., Kaprio, J., Lonnqvist, J., Poutanen, V. P., Toga, A. W., Thompson, P. M. and Cannon, T. D. Biological Psychiatry. 2008; 63(7): 26S-27S. Meeting Abstract. IF 7.154 Varjosalo, M., Bjorklund, M., Cheng, F., Syvanen, H., Kivioja, T., Kilpinen, S., Sun, Z., Kallioniemi, O., Stunnenberg, H. G., He, W. W., Ojala, P. and Taipale, J. Cell. 2008; 133(3): 537-48. IF 29.194 To allow genome-scale identification of genes that regulate cellular signaling, we cloned >90% of all human full-length protein kinase cDNAs and constructed the corresponding kinase activity-deficient mutants. To establish the utility of this resource, we tested the effect of expression of the kinases on three different cellular signaling models. In all screens, many kinases had a modest but significant effect, apparently due to crosstalk between signaling pathways. However, the strongest effects were found with known regulators and novel components, such as MAP3K10 and DYRK2, which we identified in a mammalian Hedgehog (Hh) signaling screen. DYRK2 directly phosphorylated and induced the proteasome-dependent degradation of the key Hh pathway-regulated transcription factor, GLI2. MAP3K10, in turn, affected GLI2 indirectly by modulating the activity of DYRK2 and the known Hh pathway component, GSK3beta. Our results establish kinome expression screening as a highly effective way to identify physiological signaling pathway components and genes involved in pathological signaling crosstalk. Physical activity behaviours of adults in the Greater Green Triangle region of rural Australia Vaughan, C., Kilkkinen, A., Philpot, B., Brooks, J., Schoo, A., Laatikainen, T., Chapman, A., Janus, E. D. and Dunbar, J. A. Australian Journal of Rural Health. 2008; 16(2): 92-99. Article. Objective: To assess physical activity (PA) behaviours of adults in rural Australia. Design and setting: Three cross-sectional surveys in the Greater Green Triangle area covering the south-east of South Australia (Limestone Coast), and south-west (Corangamite Shire) and north-west (Wimmera) of Victoria during 2004-2006. Participants: A total of 1546 persons, aged 2574 years, randomly selected from the electoral roll. Main outcome measures: Overall PA, leisure-time PA, occupational PA, active commuting and moderate-to-vigorous PA. Results: Approximately 80% of participants, more women than men, engaged in 30 minutes or more of daily PA. Only 30% (95% CI 26.3, 33.0) of men and 21% (95% CI 18.3, 23.9) of women did moderate-to-vigorous PA for at least 20-30 minutes four or more times a week. In leisure time, most participants were moderately active; almost one-fifth were inactive and another fifth highly active. Two-thirds of men engaged in high-level occupational PA, compared with one-sixth of women. Only 30% of participants actively commuted to work. There was a tendency for a positive association between income level and leisure-time PA. Conclusions: One-fifth of adults in rural Australia were inactive. While there was a high prevalence of participants who engaged in daily PA, few did so at moderate-to-vigorous intensity to achieve health benefits. As occupational PA is difficult to change, improvements in levels of PA are more likely during leisure-time and for some people by engaging in commuting PA. |