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- Christopoulos, Arthur, et al.
(author)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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In: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
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Research review (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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- Alexander, Stephen P. H., et al.
(author)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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In: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Journal article (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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- Kukkonen, J., et al.
(author)
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Towards a Comprehensive Evaluation of the Environmental and Health Impacts of Shipping Emissions
- 2022
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In: Springer Proceedings in Complexity. - Cham : Springer International Publishing. - 2213-8684 .- 2213-8692. ; , s. 329-336
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Conference paper (peer-reviewed)abstract
- We present a new concept for marine research, applied in the EU-funded project EMERGE, “Evaluation, control and Mitigation of the EnviRonmental impacts of shippinG Emissions” (2020–2024; https://emerge-h2020.eu/ ). For the first time, both the various marine and atmospheric impacts of the shipping sector have been and will be comprehensively analyzed, using a concerted modelling and measurements framework. The experimental part of the project focuses on five European geographical case studies in different ecologically vulnerable regions, and a mobile onboard case study. The EMERGE consortium has also developed a harmonised and integrated modelling framework to assess the combined impacts of shipping emissions, both (i) on the marine ecosystems and (ii) the atmospheric environment. The first results include substantial refinements of a range of models to be applied, especially those for the STEAM and OpenDrift models. In particular, the STEAM (Ship Traffic Emission Assessment Model) model has been extended to allow for the effects of atmospheric and oceanographic factors on the fuel consumption and emissions of the ships. The OpenDrift model has been improved to take into account the partitioning, degradation, and volatilization of pollutants in water. The predicted emission and discharge values have been used as input for both regional scale atmospheric dispersion models, such as WRF-CMAQ (Weather Research and Forecasting—Community Multiscale Air Quality Model) and SILAM (System for Integrated modeLling of Atmospheric composition), and water quality and circulation models, such as OpenDrift (Open source model for the drifting of substances in the ocean) and Delft3D (oceanographic model). The case study regions are Eastern Mediterranean, Northern Adriatic Sea, the Lagoon of Aveiro, the Solent Strait and the Öresund Strait. We have also conducted a substantial part of the experimental campaigns scheduled in the project. The final assessment will include the benefits and costs of control and mitigation options affecting water quality, air pollution exposure, health impacts, climate forcing, and ecotoxicological effects and bioaccumulation of pollutants in marine biota.
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- Van den Brink, P. J., et al.
(author)
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Toward sustainable environmental quality: Priority research questions for Europe
- 2018
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In: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 37:9, s. 2281-2295
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Journal article (peer-reviewed)abstract
- The United Nations' Sustainable Development Goals have been established to end poverty, protect the planet, and ensure prosperity for all. Delivery of the Sustainable Development Goals will require a healthy and productive environment. An understanding of the impacts of chemicals which can negatively impact environmental health is therefore essential to the delivery of the Sustainable Development Goals. However, current research on and regulation of chemicals in the environment tend to take a simplistic view and do not account for the complexity of the real world, which inhibits the way we manage chemicals. There is therefore an urgent need for a step change in the way we study and communicate the impacts and control of chemicals in the natural environment. To do this requires the major research questions to be identified so that resources are focused on questions that really matter. We present the findings of a horizon-scanning exercise to identify research priorities of the European environmental science community around chemicals in the environment. Using the key questions approach, we identified 22 questions of priority. These questions covered overarching questions about which chemicals we should be most concerned about and where, impacts of global megatrends, protection goals, and sustainability of chemicals; the development and parameterization of assessment and management frameworks; and mechanisms to maximize the impact of the research. The research questions identified provide a first-step in the path forward for the research, regulatory, and business communities to better assess and manage chemicals in the natural environment. Environ Toxicol Chem 2018;37:2281-2295. (c) 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
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- Phillips, Helen R. P., et al.
(author)
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Global distribution of earthworm diversity
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6464, s. 480-
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Journal article (peer-reviewed)abstract
- Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
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- Plyusnin, A, et al.
(author)
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Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents
- 1997
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In: Journal of clinical microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 35:5, s. 1090-1096
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Journal article (peer-reviewed)abstract
- Reverse transcription-PCR was used to analyze specimens from 20 Finnish nephropathia epidemica (NE) patients hospitalized during the period from October 1994 to January 1995. Blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of Puumala hantavirus (PUU). PCR positivity of the specimens from the patients correlated well with the HLA-DRB1*0301 and HLA B8 alleles, which previously were shown to associate with severe courses of NE. Genetic analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.
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- Raaschou-Nielsen, O., et al.
(author)
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Particulate matter air pollution components and risk for lung cancer
- 2016
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 87, s. 66-73
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Journal article (peer-reviewed)abstract
- Background: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. Methods: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. Results: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 125; 95% Cl, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m3), PMio S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PMio and PM2.5 and lung cancer were largely explained by PM2.5 S. Conclusions: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.
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- Ali, M, et al.
(author)
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Protocol for the development of the international population registry for aphasia after stroke (I-PRAISE)
- 2022
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In: Aphasiology. - : Informa UK Limited. - 0268-7038 .- 1464-5041. ; 36:4, s. 534-554
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Journal article (peer-reviewed)abstract
- Background: We require high-quality information on the current burden, the types of therapy and resources available, methods of delivery, care pathways and long-term outcomes for people with aphasia.Aim: To document and inform international delivery of post-stroke aphasia treatment, to optimise recovery and reintegration of people with aphasia.Methods & Procedures: Multi-centre, prospective, non-randomised, open study, employing blinded outcome assessment, where appropriate, including people with post-stroke aphasia, able to attend for 30 minutes during the initial language assessment, at first contact with a speech and language therapist for assessment of aphasia at participating sites. There is no study-mandated intervention. Assessments will occur at baseline (first contact with a speech and language therapist for aphasia assessment), discharge from Speech and Language Therapy (SLT), 6 and 12-months post-stroke. Our primary outcome is changed from baseline in the Amsterdam Nijmegen Everyday Language Test (ANELT/Scenario Test for participants with severe verbal impairments) at 12-months post-stroke. Secondary outcomes at 6 and 12 months include the Therapy Outcome Measure (TOMS), Subjective Index of Physical and Social Outcome (SIPSO), Aphasia Severity Rating Scale (ASRS), Western Aphasia Battery Aphasia Quotient (WAB-AQ), stroke and aphasia quality of life scale (SAQoL-39), European Quality of Life Scale (EQ-5D), lesion description, General Health Questionnaire (GHQ-12), resource use, and satisfaction with therapy provision and success. We will collect demography, clinical data, and therapy content. Routine neuroimaging and medication administration records will be accessed where possible; imaging will be pseudonymised and transferred to a central reading centre. Data will be collected in a central registry. We will describe demography, stroke and aphasia profiles and therapies available. International individual participant data (IPD) meta-analyses will examine treatment responder rates based on minimal detectable change & clinically important changes from baseline for primary and secondary outcomes at 6 and 12 months. Multivariable meta-analyses will examine associations between demography, therapy, medication use and outcomes, considering service characteristics. Where feasible, costs associated with treatment will be reported. Where available, we will detail brain lesion size and site, and examine correlations with SLT and language outcome at 12 months.Conclusion: International differences in care, resource utilisation and outcomes will highlight avenues for further aphasia research, promote knowledge sharing and optimise aphasia rehabilitation delivery. IPD meta-analyses will enhance and expand understanding, identifying cost-effective and promising approaches to optimise rehabilitation to benefit people with aphasia.
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- Brady, MC, et al.
(author)
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Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis
- 2022
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In: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 17:10, s. 1067-1077
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Journal article (peer-reviewed)abstract
- Stroke rehabilitation interventions are routinely personalized to address individuals’ needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild–moderate/ moderate–severe based on language outcomes’ median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants’ greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3–4 SLT-h/week; ⩾ 50 hours). For moderate–severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild–moderate participants’ greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males’ greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week. Conclusions: We observed a treatment response in most subgroups’ overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild–moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate–severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.
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- Hussein, T., et al.
(author)
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Evaluation and modeling of the size fractionated aerosol particle number concentration measurements nearby a major road in Helsinki - Part II : Aerosol measurements within the SAPPHIRE project
- 2007
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 7:15, s. 4081-4094
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Journal article (peer-reviewed)abstract
- This study presents an evaluation and modeling exercise of the size fractionated aerosol particle number concentrations measured nearby a major road in Helsinki during 23 August-19 September 2003 and 14 January-11 February 2004. The available information also included electronic traffic counts, on-site meteorological measurements, and urban background particle number size distribution measurement. The ultrafine particle (UFP, diameter < 100 nm) number concentrations at the roadside site were approximately an order of magnitude higher than those at the urban background site during daytime and downwind conditions. Both the modal structure analysis of the particle number size distributions and the statistical correlation between the traffic density and the UFP number concentrations indicate that the UFP were evidently from traffic related emissions. The modeling exercise included the evolution of the particle number size distribution nearby the road during downwind conditions. The model simulation results revealed that the evaluation of the emission factors of aerosol particles might not be valid for the same site during different time.
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- Pohjola, M. A., et al.
(author)
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Evaluation and modelling of the size fractionated aerosol particle number concentration measurements nearby a major road in Helsinki - Part I : Modelling results within the LIPIKA project
- 2007
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 7:15, s. 4065-4080
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Journal article (peer-reviewed)abstract
- A field measurement campaign was conducted near a major road ""Itavayla in an urban area in Helsinki in 17-20 February 2003. Aerosol measurements were conducted using a mobile laboratory ""Sniffer"" at various distances from the road, and at an urban background location. Measurements included particle size distribution in the size range of 7 nm-10 mu m (aerodynamic diameter) by the Electrical Low Pressure Impactor (ELPI) and in the size range of 3-50 nm ( mobility diameter) by Scanning Mobility Particle Sizer (SMPS), total number concentration of particles larger than 3 nm detected by an ultrafine condensation particle counter (UCPC), temperature, relative humidity, wind speed and direction, driving route of the mobile laboratory, and traffic density on the studied road. In this study, we have compared measured concentration data with the predictions of the road network dispersion model CAR-FMI used in combination with an aerosol process model MONO32. For model comparison purposes, one of the cases was additionally computed using the aerosol process model UHMA, combined with the CAR-FMI model. The vehicular exhaust emissions, and atmospheric dispersion and transformation of fine and ultrafine particles was evaluated within the distance scale of 200m (corresponding to a time scale of a couple of minutes). We computed the temporal evolution of the number concentrations, size distributions and chemical compositions of various particle size classes. The atmospheric dilution rate of particles is obtained from the roadside dispersion model CAR-FMI. Considering the evolution of total number concentration, dilution was shown to be the most important process. The influence of coagulation and condensation on the number concentrations of particle size modes was found to be negligible on this distance scale. Condensation was found to affect the evolution of particle diameter in the two smallest particle modes. The assumed value of the concentration of condensable organic vapour of 10(12) molecules cm(-3) was shown to be in a disagreement with the measured particle size evolution, while the modelling runs with the concentration of condensable organic vapour of 10(9)-10(10) molecules cm(-3) resulted in particle sizes that were closest to the measured values.
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- Allaouat, S, et al.
(author)
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Long-term exposure to ambient fine particulate matter originating from traffic and residential wood combustion and the prevalence of depression
- 2021
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In: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 75:11, s. 1111-1116
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Journal article (peer-reviewed)abstract
- Air pollution has been suggested to be associated with depression. However, current evidence is conflicting, and no study has considered different sources of ambient particulate matter with an aerodynamic diameter below 2.5 µm (PM2.5). We evaluated the associations of long-term exposure to PM2.5 from road traffic and residential wood combustion with the prevalence of depression in the Helsinki region, Finland.MethodsWe conducted a cross-sectional analysis based on the Helsinki Capital Region Environmental Health Survey 2015–2016 (N=5895). Modelled long-term outdoor concentrations of PM2.5 were evaluated using high-resolution emission and dispersion modelling on an urban scale and linked to the home addresses of study participants. The outcome was self-reported doctor-diagnosed or treated depression. We applied logistic regression and calculated the OR for 1 μg/m3 increase in PM2.5, with 95% CI. Models were adjusted for potential confounders, including traffic noise and urban green space.ResultsOf the participants, 377 reported to have been diagnosed or treated for depression by a doctor. Long-term exposure to PM2.5 from road traffic (OR=1.23, 95% CI 0.86 to 1.73; n=5895) or residential wood combustion (OR=0.78, 95% CI 0.43 to 1.41; n=5895) was not associated with the prevalence of depression. The estimates for PM2.5 from road traffic were elevated, but statistically non-significant, for non-smokers (OR=1.38, 95% CI 0.94 to 2.01; n=4716).ConclusionsWe found no convincing evidence of an effect of long-term exposure to PM2.5 from road traffic or residential wood combustion on depression.
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- Beelen, Rob, et al.
(author)
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Natural-Cause Mortality and Long-Term Exposure to Particle Components : An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 525-533
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Research review (peer-reviewed)abstract
- Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.
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28. |
- de Hoogh, Kees, et al.
(author)
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Comparing land use regression and dispersion modelling to assess residential exposure to ambient air pollution for epidemiological studies
- 2014
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 73, s. 382-392
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Journal article (peer-reviewed)abstract
- Background: Land-use regression (LUR) and dispersion models (DM) are commonly used for estimating individual air pollution exposure in population studies. Few comparisons have however been made of the performance of these methods. Objectives: Within the European Study of Cohorts for Air Pollution Effects (ESCAPE) we explored the differences between LUR and DM estimates for NO2, PM10 and PM2.5. Methods: The ESCAPE study developed LUR models for outdoor air pollution levels based on a harmonised monitoring campaign. In thirteen ESCAPE study areas we further applied dispersion models. We compared LUR and DM estimates at the residential addresses of participants in 13 cohorts for NO2; 7 for PM10 and 4 for PM2.5. Additionally, we compared the DM estimates with measured concentrations at the 20-40 ESCAPE monitoring sites in each area. Results: The median Pearson R (range) correlation coefficients between LUR and DM estimates for the annual average concentrations of NO2, PM10 and PM2.5 were 0.75 (0.19-0.89), 0.39 (0.23-0.66) and 0.29 (0.22-0.81) for 112,971 (13 study areas), 69,591 (7) and 28,519(4) addresses respectively. The median Pearson R correlation coefficients (range) between DM estimates and ESCAPE measurements were of 0.74(0.09-0.86) for NO2; 0.58 (0.36-0.88) for PM10 and 0.58 (0.39-0.66) for PM2.5. Conclusions: LUR and dispersion model estimates correlated on average well for NO2 but only moderately for PM10 and PM2.5, with large variability across areas. DM predicted a moderate to large proportion of the measured variation for NO2 but less for PM10 and PM2.5.
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- Korhonen, Laura, et al.
(author)
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Hippocalcin protects against caspase-12-induced and age-dependent neuronal degeneration
- 2005
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In: Molecular and Cellular Neuroscience. - Uppsala Univ, Ctr Biomed, Dept Neurosci, Neurobiol Unit, S-75123 Uppsala, Sweden. Uppsala Univ, Ctr Biomed, Dept Neurosci, Unit Physiol, S-75123 Uppsala, Sweden. Toho Univ, Sch Med, Dept Physiol, Ohta Ku, Tokyo 1438540, Japan. Minerva Med Res Inst, Biomedicum Helsinki, FIN-00290 Helsinki, Finland. : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1044-7431 .- 1095-9327. ; 28:1, s. 85-95
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Journal article (peer-reviewed)abstract
- Hippocalcin is a neuronal calcium binding protein, but its physiological function in brain is unknown. We show here that hippocampal neurons from hippocalcin-deficient mice are more vulnerable to degeneration, particularly using thapsigargin, elevating intracellular calcium. Caspase-12 was activated in neurons lacking hippocalcin, while calpain was unchanged. Neuronal viability was accompanied by endoplasmic reticulum (ER) stress and a change in the relative induction of the ER chaperone, BiP/GRP78. Neuronal apoptosis inhibitor protein (NAIP), known to interact with hippocalcin, was not altered, but hippocampal neurons from gene-deleted mice were more sensitive to excitotoxicity caused by kainic acid. In addition, an age-dependent increase in neurodegeneration occurred in the gene-deleted mice, showing that hippocalcin contributes to neuronal viability during aging. (C) 2004 Elsevier Inc. All rights reserved.
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- Lagerström, Malin C., et al.
(author)
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Origin of the prolactin-releasing hormone (PRLH) receptors : Evidence of coevolution between PRLH and a redundant neuropeptide Y receptor during vertebrate evolution
- 2005
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In: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 85:6, s. 688-703
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Journal article (peer-reviewed)abstract
- We present seven new vertebrate homologs of the prolactin-releasing hormone receptor (PRLHR) and show that these are found as two separate subtypes, PRLHR1 and PRLHR2. Analysis of a number of vertebrate sequences using phylogeny, pharmacology, and paralogon analysis indicates that the PRLHRs are likely to share a common ancestry with the neuropeptide Y (NPY) receptors. Moreover, a micromolar level of NPY was able to bind and inhibit completely the PRLH-evoked response in PRLHR1-expressing cells. We suggest that an ancestral PRLH peptide started coevolving with a redundant NPY binding receptor, which then became PRLHR, approximately 500 million years ago. The PRLHR1 subtype was shown to have a relatively high evolutionary rate compared to receptors with fixed peptide preference, which could indicate a drastic change in binding preference, thus supporting this hypothesis. This report suggests how gene duplication events can lead to novel peptide ligand/receptor interactions and hence spur the evolution of new physiological functions.
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39. |
- Lindholm, D, et al.
(author)
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Neuronal apoptosis inhibitory protein : structural requirements for hippocalcin binding and effects on survival of NGF-denendent sympathetic neurons
- 2002
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In: Biochimica et Biophysica Acta - Proteins and Proteomics. - : ELSEVIER SCIENCE BV. - 1570-9639 .- 1878-1454. ; 1600:1-2, s. 138-147
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Journal article (peer-reviewed)abstract
- Neuronal apoptosis inhibitory protein (NAIP) has been linked to the inherited disease, spinal muscular atrophy (SMA), which occurs in children with degeneration of the motorneurons. In the nervous system, NAIP is expressed by specific classes of neurons including spinal -motorneurons. Recently, NAIP was shown to interact with hippocalcin, which belongs to the neuronal calcium sensor (NCS) protein family. Here we-have studied this interaction in more detail, using deletions and a mutagenesis of the third baculovirus inhibitory repeat (BIR) motif in NAIP, and functional assays for neuronal death. The results showed that specific amino acids and the zinc finger domain in BIR3 are needed for efficient interaction of NAIP with hippocalcin. Cotransfections of NAIP-BIR3 and hippocalcin resulted in translocation and colocalisation of the two proteins in neuroblastoma cells. This was accompanied by an enhanced resistance towards cell death induced by high levels of calcium. In contrast, expression of NAIP-BIR3 and hippocalcin in sympathetic neurons did not protect against death induced by nerve growth factor (NGF) withdrawal. The results demonstrate a functional interaction of hippocalcin with NAIP-BIR3, which in neuroblastoma cells leads to rescue of cells after high intracellular calcium, but which in sympathetic neurons had no significant effect. The results indicate that NAIP in conjunction with hippocalcin can affect the survival of some, but not all neural cells, and this interaction may play a role in the neurodegenerative processes in SMA, and possible other human disorders. (C) 2002 Elsevier Science B.V All rights reserved.
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40. |
- Lund, P E, et al.
(author)
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The orexin OX1 receptor activates a novel Ca2+ influx pathway necessary for coupling to phospholipase C.
- 2000
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:40, s. 30806-12
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Journal article (peer-reviewed)abstract
- Ca(2+) elevations in Chinese hamster ovary cells stably expressing OX(1) receptors were measured using fluorescent Ca(2+) indicators fura-2 and fluo-3. Stimulation with orexin-A led to pronounced Ca(2+) elevations with an EC(50) around 1 nm. When the extracellular [Ca(2+)] was reduced to a submicromolar concentration, the EC(50) was increased 100-fold. Similarly, the inositol 1,4,5-trisphosphate production in the presence of 1 mm external Ca(2+) was about 2 orders of magnitude more sensitive to orexin-A stimulation than in low extracellular Ca(2+). The shift in the potency was not caused by depletion of intracellular Ca(2+) but by a requirement of extracellular Ca(2+) for production of inositol 1,4,5-trisphosphate. Fura-2 experiments with the "Mn(2+)-quench technique" indicated a direct activation of a cation influx pathway by OX(1) receptor independent of Ca(2+) release or pool depletion. Furthermore, depolarization of the cells to +60 mV, which almost nullifies the driving force for Ca(2+) entry, abolished the Ca(2+) response to low concentrations of orexin-A. The results thus suggest that OX(1) receptor activation leads to two responses, (i) a Ca(2+) influx and (ii) a direct stimulation of phospholipase C, and that these two responses converge at the level of phospholipase C where the former markedly enhances the potency of the latter.
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41. |
- Marschan, E, et al.
(author)
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Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with igE sensitization
- 2008
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 19:2, s. 132-139
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Journal article (peer-reviewed)abstract
- Risk of allergic diseases has been linked to abnormal patterns of fetal immune development, suggesting that priming of the immune system may occur in utero. The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells (CBMC) shows association with allergic diseases and IgE sensitization at 2 yr of age, and to study the effect of maternal probiotic supplementation on CBMC immune responses. CBMC were isolated from 98 neonates in a randomized double-blinded intervention study. CBMC were stimulated with beta-lactoglobulin, and phytohemaglutinin (PHA). Secretion of interferon-gamma (IFN-γ), interleukin-5 (IL-5), and IL-13 was measured by an ELISA; IL-2, IL-4, and IL-10 by a cytokine bead assay. T-cell polarization-associated IL-4 receptor and IL-12R expressions, and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR. The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age, and with the maternal probiotic or placebo supplementation. PHA-stimulated GATA-3 expression and IL-2 secretion in CBMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized, non-allergic children (p = 0.03 and 0.026). PHA-induced expression of GATA-3 correlated with IL-5 (p = 0.003, r = 0.300) and IL-13 (p = 0.007, r = 0.278) secretion of CBMC, and IL-5 secretion of β-lactoglobulin-stimulated CBMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized, non-allergic children (p = 0.013). Probiotic bacteria had no effect on CBMC immune responses. In CBMC-enhanced induction of GATA-3, which activates several Th2 cytokines genes, was a risk factor for IgE sensitization. The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens.
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43. |
- Moilanen, Lauri J., et al.
(author)
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TRPA1 Contributes to the Acute Inflammatory Response and Mediates Carrageenan-Induced Paw Edema in the Mouse
- 2012
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 2
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Journal article (peer-reviewed)abstract
- Transient receptor potential ankyrin 1 (TRPA1) is an ion channel involved in thermosensation and nociception. TRPA1 is activated by exogenous irritants and also by oxidants formed in inflammatory reactions. However, our understanding of its role in inflammation is limited. Here, we tested the hypothesis that TRPA1 is involved in acute inflammatory edema. The TRPA1 agonist allyl isothiocyanate (AITC) induced inflammatory edema when injected intraplantarly to mice, mimicking the classical response to carrageenan. Interestingly, the TRPA1 antagonist HC-030031 and the cyclo-oxygenase (COX) inhibitor ibuprofen inhibited not only AITC but also carrageenan-induced edema. TRPA1-deficient mice displayed attenuated responses to carrageenan and AITC. Furthermore, AITC enhanced COX-2 expression in HEK293 cells transfected with human TRPA1, a response that was reversed by HC-030031. This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation.
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- Ryösä, A., et al.
(author)
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Acute Cuff Tear Repair Trial (ACCURATE) : Protocol for a multicentre, randomised, placebo-controlled trial on the efficacy of arthroscopic rotator cuff repair
- 2019
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:5
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Journal article (peer-reviewed)abstract
- Introduction Rotator cuff tear is a very common and disabling condition that can be related to acute trauma. Rotator cuff tear surgery is a well-established form of treatment in acute rotator cuff tears. Despite its widespread use and almost a gold standard position, the efficacy of an arthroscopic rotator cuff repair is still unknown. The objective of this trial is to investigate the difference in outcome between arthroscopic rotator cuff repair and inspection of the shoulder joint defined as placebo surgery in patients 45–70 years of age with an acute rotator tear related to trauma.Methods and analysis Acute Cuff Tear Repair Trial (ACCURATE) is a randomised, placebo-controlled, multicentre efficacy trial with sample size of 180 patients. Concealed allocation is done in 1:1 ratio. The randomisation is stratified according to participating hospital, gender and baseline Western Ontario Rotator Cuff Index (WORC). Both groups receive the same standardised postoperative treatment and physiotherapy. The primary outcome measure is the change in WORC score from baseline to 2-year follow-up. Secondary outcome measures include Constant-Murley Score, the Numerical Rating Scale for pain, subjective patient satisfaction and the health-related quality of life instrument 15 dimensions (15D). Patients and outcome assessors are blinded from the allocated intervention. The primary analysis of results will be conducted according to intention-to-treat analysis.Ethics and dissemination The study protocol for this clinical trial has been approved by the Ethics Committee of the Hospital District of Southwest Finland and Regional Ethics Committee in Linköping Sweden and Regional Committees for Medical and Health Research Ethics South East in Norway. Every recruiting centre will apply local research approvals. The results of this study will be submitted for publication in peer-reviewed journals.
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