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Sökning: WFRF:(Hedlund R.)

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  • Murray, Alison E., et al. (författare)
  • Roadmap for naming uncultivated Archaea and Bacteria
  • 2020
  • Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
  • Tidskriftsartikel (refereegranskat)abstract
    • The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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  • Setälä, H., et al. (författare)
  • Urban and agricultural soils : Conflicts and trade-offs in the optimization of ecosystem services
  • 2014
  • Ingår i: Urban Ecosystems. - : Springer Science and Business Media LLC. - 1083-8155 .- 1573-1642. ; 17:1, s. 239-253
  • Tidskriftsartikel (refereegranskat)abstract
    • On-going human population growth and changing patterns of resource consumption are increasing global demand for ecosystem services, many of which are provided by soils. Some of these ecosystem services are linearly related to the surface area of pervious soil, whereas others show non-linear relationships, making ecosystem service optimization a complex task. As limited land availability creates conflicting demands among various types of land use, a central challenge is how to weigh these conflicting interests and how to achieve the best solutions possible from a perspective of sustainable societal development. These conflicting interests become most apparent in soils that are the most heavily used by humans for specific purposes: urban soils used for green spaces, housing, and other infrastructure and agricultural soils for producing food, fibres and biofuels. We argue that, despite their seemingly divergent uses of land, agricultural and urban soils share common features with regards to interactions between ecosystem services, and that the trade-offs associated with decision-making, while scale- and context-dependent, can be surprisingly similar between the two systems. We propose that the trade-offs within land use types and their soil-related ecosystems services are often disproportional, and quantifying these will enable ecologists and soil scientists to help policy makers optimizing management decisions when confronted with demands for multiple services under limited land availability.
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  • Abbott, Allan, et al. (författare)
  • The effectiveness of physiotherapeutic rehabilitation and issues of outcome prediction after lumber fusion surgery.
  • 2011
  • Ingår i: Proceedings of the WCPT Congress, Amsterdam Netherlands.. - : World Confederation of Physical Therapy. ; , s. 20-
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Purpose: The primary purpose was to analyse the short and long term effectiveness of physiotherapeutic rehabilitation programs performed during the first 3 month after lumbar fusion surgery. A secondary purpose was to analyse factors predicting long-term disability, back pain and health related quality of life (HRQOL) outcomes after lumbar fusion.Relevance: The study provides evidence for the effectiveness of early physiotherapy after lumbar fusion. Furthermore improved knowledge of predictive factors can help physiotherapist in the screening of lumbar fusion candidates and the individualised implementation of pre-surgical and post-surgical interventions.Participants: A total of 107 patients were recruited from the Karolinska University Hospital's Orthopaedic Clinic, Stockholm, Sweden. The inclusion criteria were: men and women aged between 18 and 65 years with a >12 month history of back pain and/or sciatica; a primary diagnosis of spinal stenosis, degenerative or isthmic spondylolisthesis or degenerative disc disease; selected for lumbar fusion with or without decompression; competence in the Swedish language. The criteria for exclusion were: previous lumbar fusion, rheumatoid arthritis and ankylosing spondylitis.Methods: An open book randomised controlled trial with pre-surgical and post-surgical measures at 3, 6, 12 and 24-36 months was performed to investigate the effectiveness of a psychomotor therapy focusing on cognition, behaviour and motor relearning compared to exercise therapy focusing on strength and conditioning, applied during the first 3 months after lumbar fusion. Randomisation allocated 53 patients to psychomotor therapy and 54 patients to exercise therapy. The Oswestry disability index (ODI) was the primary outcome measure. Secondary measures included the Visual analogue scale for back pain (VAS), European quality of life questionnaire (EQ5D), as well as other clinical, psychological and work related variables.Analysis: A total of 78 patients were needed assuming a power = 80%. Patient compliance was analysed and an intention to treat principle applied to data analysis. For statistical comparison between the 2 independent groups, analysis of covariance was used. Categorical regression with optimal scaling transformation, elastic net regularization and bootstrapping were used to investigate pre-surgical predictor variables and address predictive model validity.Results: Follow-up rates were 93% at 12 months and 81% at 24-36 months after surgery. Psychomotor therapy improved functional disability, self-efficacy, outcome expectancy and fear of movement/(re)injury significantly more than exercise therapy at respective follow-up occasions. Pre-surgical control over pain significantly predicted functional disability and HRQOL. Pre-surgical catastrophizing and leg pain intensity significantly predicted functional disability and back pain while the pre-surgical lasegue test significantly predicted back pain. The implementation of post-operative psychomotor therapy also significantly predicted functional disability while pre-surgical outcome expectations significantly predicted HRQOL.Conclusions: The study shows that post-operative rehabilitation can be safely implemented during the first 3 months after lumbar fusion and should include measures to modify psychological as well as motor functions. The study also demonstrates the importance of pre-surgical psychological factors, leg pain intensity, the lasegue test and post-operative psychomotor therapy in the predictions of functional disability, back pain and HRQOL related outcomes.Implications: Physiotherapist should screen patients pain, psychological factors and neuromusculoskeletal system pre-surgically and rehabilitate patients with early psychomotor therapy after lumbar fusion.
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  • Bowers, Robert M., et al. (författare)
  • Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea
  • 2017
  • Ingår i: Nature Biotechnology. - : NATURE PUBLISHING GROUP. - 1087-0156 .- 1546-1696. ; 35:8, s. 725-731
  • Tidskriftsartikel (refereegranskat)abstract
    • We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequence (MIxS). The standards are the Minimum Information about a Single Amplified Genome (MISAG) and the Minimum Information about a Metagenome-Assembled Genome (MIMAG), including, but not limited to, assembly quality, and estimates of genome completeness and contamination. These standards can be used in combination with other GSC checklists, including the Minimum Information about a Genome Sequence (MIGS), Minimum Information about a Metagenomic Sequence (MIMS), and Minimum Information about a Marker Gene Sequence (MIMARKS). Community-wide adoption of MISAG and MIMAG will facilitate more robust comparative genomic analyses of bacterial and archaeal diversity.
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  • Faber, Zachary J, et al. (författare)
  • The genomic landscape of core-binding factor acute myeloid leukemias
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 48, s. 1551-1556
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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  • Fritzell, Peter, et al. (författare)
  • Cost-effectiveness of lumbar fusion and nonsurgical treatment for chronic low back pain in the Swedish lumbar spine study : A multicenter, randomized, controlled trial from the Swedish Lumbar Spine Study Group
  • 2004
  • Ingår i: Spine. - : Lippincott Williams & Wilkins. - 0362-2436 .- 1528-1159. ; 29:4, s. 421-434
  • Tidskriftsartikel (refereegranskat)abstract
    • Study Design. A cost-effectiveness study was performed from the societal and health care perspectives. Objective. To evaluate the costs-effectiveness of lumbar fusion for chronic low back pain (CLBP) during a 2-year follow-up. Summary of Background Data. A full economic evaluation comparing costs related to treatment effects in patients with CLBP is lacking. Patients and Methods. A total of 284 of 294 patients with CLBP for at least 2 years were randomized to either lumbar fusion or a nonsurgical control group. Costs for the health care sector ( direct costs), and costs associated with production losses ( indirect costs) were calculated. Societal total costs were identified as the sum of direct and indirect costs. Treatment effects were measured using patient global assessment of improvement, back pain ( VAS), functional disability (Owestry), and return to work. Results. The societal total cost per patient ( standard deviations) in the surgical group was significantly higher than in the nonsurgical group: Swedish kroner (SEK) 704,000 ( 254,000) vs. SEK 636,000 ( 208,000). The cost per patient for the health care sector was significantly higher for the surgical group, SEK 123,000 ( 60,100) vs. 65,200 ( 38,400) for the control group. All treatment effects were significantly better after surgery. The incremental cost-effectiveness ratio ( ICER), illustrating the extra cost per extra effect unit gained by using fusion instead of nonsurgical treatment, were for improvement: SEK 2,600 ( 600 - 5,900), for back pain: SEK 5,200 ( 1,100 - 11,500), for Oswestry: SEK 11,300 ( 1,200 - 48,000), and for return to work: SEK 4,100 ( 100 21,400). Conclusion. For both the society and the health care sectors, the 2-year costs for lumbar fusion was significantly higher compared with nonsurgical treatment but all treatment effects were significantly in favor of surgery. The probability of lumbar fusion being cost-effective increased with the value put on extra effect units gained by using surgery.
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  • Holmfeldt, Linda, et al. (författare)
  • The genomic landscape of hypodiploid acute lymphoblastic leukemia
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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  • Wasserman, D, et al. (författare)
  • Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries
  • 2020
  • Ingår i: European psychiatry : the journal of the Association of European Psychiatrists. - : Royal College of Psychiatrists. - 1778-3585. ; 63:1, s. e82-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
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  • Abrate, Alberto, et al. (författare)
  • Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression
  • 2014
  • Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 50:14, s. 2478-2488
  • Tidskriftsartikel (refereegranskat)abstract
    • Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase:: uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease.
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  • Aguila, JC, et al. (författare)
  • Cellular programming and reprogramming: sculpting cell fate for the production of dopamine neurons for cell therapy
  • 2012
  • Ingår i: Stem cells international. - : Hindawi Limited. - 1687-9678 .- 1687-966X. ; 2012, s. 412040-
  • Tidskriftsartikel (refereegranskat)abstract
    • Pluripotent stem cells are regarded as a promising cell source to obtain human dopamine neurons in sufficient amounts and purity for cell replacement therapy. Importantly, the success of clinical applications depends on our ability to steer pluripotent stem cells towards the right neuronal identity. In Parkinson disease, the loss of dopamine neurons is more pronounced in the ventrolateral population that projects to the sensorimotor striatum. Because synapses are highly specific, only neurons with this precise identity will contribute, upon transplantation, to the synaptic reconstruction of the dorsal striatum. Thus, understanding the developmental cell program of the mesostriatal dopamine neurons is critical for the identification of the extrinsic signals and cell-intrinsic factors that instruct and, ultimately, determine cell identity. Here, we review how extrinsic signals and transcription factors act together during development to shape midbrain cell fates. Further, we discuss how these same factors can be appliedin vitroto induce, select, and reprogram cells to the mesostriatal dopamine fate.
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  • Bergdahl, I A, et al. (författare)
  • Increased mortality in COPD among construction workers exposed to inorganic dust.
  • 2004
  • Ingår i: European Respiratory Journal. - 0903-1936 .- 1399-3003. ; 23:3, s. 402-406
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to find out if occupational exposure to dust, fumes or gases, especially among never-smokers, increased the mortality from chronic obstructive pulmonary disease (COPD). A cohort of 317,629 Swedish male construction workers was followed from 1971 to 1999. Exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), gases and irritants (epoxy resins, isocyanates and organic solvents), fumes (asphalt fumes, diesel exhaust and metal fumes), and wood dust was based on a job-exposure matrix. An internal control group with "unexposed" construction workers was used, and the analyses were adjusted for age and smoking. When all subjects were analysed, there was an increased mortality from COPD among those with any airborne exposure (relative risk 1.12 (95% confidence interval (CI) 1.03-1.22)). In a Poisson regression model, including smoking, age and the major exposure groups, exposure to inorganic dust was associated with an increased risk (hazard ratio (HR) 1.10 (95% CI 1.06-1.14)), especially among never-smokers (HR 2.30 (95% CI 1.07-4.96)). The fraction of COPD among the exposed attributable to any airborne exposure was estimated as 10.7% overall and 52.6% among never-smokers. In conclusion, occupational exposure among construction workers increases mortality due to chronic obstructive pulmonary disease, even among never-smokers.
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  • Bezemer, T. M., et al. (författare)
  • Divergent composition but similar function of soil food webs of individual plants: plant species and community effects
  • 2010
  • Ingår i: Ecology. - 0012-9658. ; 91:10, s. 3027-3036
  • Tidskriftsartikel (refereegranskat)abstract
    • Soils are extremely rich in biodiversity, and soil organisms play pivotal roles in supporting terrestrial life, but the role that individual plants and plant communities play in influencing the diversity and functioning of soil food webs remains highly debated. Plants, as primary producers and providers of resources to the soil food web, are of vital importance for the composition, structure, and functioning of soil communities. However, whether natural soil food webs that are completely open to immigration and emigration differ underneath individual plants remains unknown. In a biodiversity restoration experiment we first compared the soil nematode communities of 228 individual plants belonging to eight herbaceous species. We included grass, leguminous, and non-leguminous species. Each individual plant grew intermingled with other species, but all plant species had a different nematode community. Moreover, nematode communities were more similar when plant individuals were growing in the same as compared to different plant communities, and these effects were most apparent for the groups of bacterivorous, carnivorous, and omnivorous nematodes. Subsequently, we analyzed the composition, structure, and functioning of the complete soil food webs of 58 individual plants, belonging to two of the plant species, Lotus corniculatus (Fabaceae) and Plantago lanceolata (Plantaginaceae). We isolated and identified more than 150 taxa/groups of soil organisms. The soil community composition and structure of the entire food webs were influenced both by the species identity of the plant individual and the surrounding plant community. Unexpectedly, plant identity had the strongest effects on decomposing soil organisms, widely believed to be generalist feeders. In contrast, quantitative food web modeling showed that the composition of the plant community influenced nitrogen mineralization under individual plants, but that plant species identity did not affect nitrogen or carbon mineralization or food web stability. Hence, the composition and structure of entire soil food webs vary at the scale of individual plants and are strongly influenced by the species identity of the plant. However, the ecosystem functions these food webs provide are determined by the identity of the entire plant community.
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  • Chen, G, et al. (författare)
  • Single-cell analyses of X Chromosome inactivation dynamics and pluripotency during differentiation
  • 2016
  • Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 26:10, s. 1342-1354
  • Tidskriftsartikel (refereegranskat)abstract
    • Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key aspects of embryonic development. However, the underlying relationship and mechanisms among these processes remain unclear. Here, we systematically dissected these features along developmental progression using mouse embryonic stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We found that mESCs grown in a ground state 2i condition displayed transcriptomic profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem cells closely resembled the post-implantation epiblast. Sex-related gene expression varied greatly across distinct developmental states. We also identified novel markers that were highly enriched in each developmental state. Moreover, we revealed that several novel pathways, including PluriNetWork and Focal Adhesion, were responsible for the delayed progression of female EpiStem cells. Importantly, we “digitalized” XCI progression using allelic expression of active and inactive X Chromosomes and surprisingly found that XCI states exhibited profound variability in each developmental state, including the 2i condition. XCI progression was not tightly synchronized with loss of pluripotency and increase of differentiation at the single-cell level, although these processes were globally correlated. In addition, highly expressed genes, including core pluripotency factors, were in general biallelically expressed. Taken together, our study sheds light on the dynamics of XCI progression and the asynchronicity between pluripotency, differentiation, and XCI.
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  • Correia, Jorge C., et al. (författare)
  • Muscle-secreted neurturin couples myofiber oxidative metabolism and slow motor neuron identity
  • 2021
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:11, s. 2215-2230
  • Tidskriftsartikel (refereegranskat)abstract
    • Endurance exercise promotes skeletal muscle vascularization, oxidative metabolism, fiber-type switching, and neuromuscular junction integrity. Importantly, the metabolic and contractile properties of the muscle fiber must be coupled to the identity of the innervating motor neuron (MN). Here, we show that muscle-derived neurturin (NRTN) acts on muscle fibers and MNs to couple their characteristics. Using a muscle-specific NRTN transgenic mouse (HSA-NRTN) and RNA sequencing of MN somas, we observed that retrograde NRTN signaling promotes a shift toward a slow MN identity. In muscle, NRTN increased capillary density and oxidative capacity and induced a transcriptional reprograming favoring fatty acid metabolism over glycolysis. This combination of effects on muscle and MNs makes HSA-NRTN mice lean with remarkable exercise performance and motor coordination. Interestingly, HSA-NRTN mice largely recapitulate the phenotype of mice with muscle-specific expression of its upstream regulator PGC-1a1. This work identifies NRTN as a myokine that couples muscle oxidative capacity to slow MN identity.
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  • de Vries, Franciska T., et al. (författare)
  • Soil food web properties explain ecosystem services across European land use systems
  • 2013
  • Ingår i: Proceedings of the National Academy of Sciences. - Washington, DC : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 110:35, s. 14296-14301
  • Tidskriftsartikel (refereegranskat)abstract
    • Intensive land use reduces the diversity and abundance of many soil biota, with consequences for the processes that they govern and the ecosystem services that these processes underpin. Relationships between soil biota and ecosystem processes have mostly been found in laboratory experiments and rarely are found in the field. Here, we quantified, across four countries of contrasting climatic and soil conditions in Europe, how differences in soil food web composition resulting from land use systems (intensive wheat rotation, extensive rotation, and permanent grassland) influence the functioning of soils and the ecosystem services that they deliver. Intensive wheat rotation consistently reduced the biomass of all components of the soil food web across all countries. Soil food web properties strongly and consistently predicted processes of C and N cycling across land use systems and geographic locations, and they were a better predictor of these processes than land use. Processes of carbon loss increased with soil food web properties that correlated with soil C content, such as earthworm biomass and fungal/bacterial energy channel ratio, and were greatest in permanent grassland. In contrast, processes of N cycling were explained by soil food web properties independent of land use, such as arbuscular mycorrhizal fungi and bacterial channel biomass. Our quantification of the contribution of soil organisms to processes of C and N cycling across land use systems and geographic locations shows that soil biota need to be included in C and N cycling models and highlights the need to map and conserve soil biodiversity across the world.
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  • Dohlsten, M, et al. (författare)
  • Lymphocyte subpopulations and lymphokine production in children with constitutional aplastic anemia
  • 1988
  • Ingår i: Pediatric Hematology & Oncology. - : Informa UK Limited. - 1521-0669 .- 0888-0018. ; 5:2, s. 143-151
  • Tidskriftsartikel (refereegranskat)abstract
    • The expression of lymphocyte surface markers as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN) by mitogen-stimulated peripheral blood mononuclear cells (MNC) have been studied in five children with constitutional aplastic anemia. A significantly reduced T4/T8 ratio was found and two of five patients also had a reduced percentage of B cells. One patient had a high percentage of HLA-DR positive T8+ cells, very suggestive of a high degree of circulating activated T suppressor/cytotoxic cells. IL-2 production was reduced in two patients, whereas IFN production was only reduced in one of these. The abnormalities found correlate with the duration of the bone marrow failure. The patients with the longest duration of bone marrow failure also exhibited the lowest T4/T8 ratio. No spontaneous IFN production was detected in any of the patients. There was no clinical benefit or reversal of the immune abnormalities during and following treatment with cimetidine and cyclosporine A in two patients.
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  • Ebrahimi, Sheida, et al. (författare)
  • Application of PET/MRI in Gynecologic Malignancies
  • 2024
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 16:8
  • Forskningsöversikt (refereegranskat)abstract
    • Simple Summary This article reviews the value of Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in evaluating female pelvic cancers. It also provides a comparative analysis of PET/MRI with other imaging modalities in the context of female pelvic malignancies and outlines their respective strengths and limitations. The aim of this narrative review is to introduce to clinicians up and coming technology and how it may be valuable to their assessment of female pelvic cancers.Abstract The diagnosis, treatment, and management of gynecologic malignancies benefit from both positron emission tomography/computed tomography (PET/CT) and MRI. PET/CT provides important information on the local extent of disease as well as diffuse metastatic involvement. MRI offers soft tissue delineation and loco-regional disease involvement. The combination of these two technologies is key in diagnosis, treatment planning, and evaluating treatment response in gynecological malignancies. This review aims to assess the performance of PET/MRI in gynecologic cancer patients and outlines the technical challenges and clinical advantages of PET/MR systems when specifically applied to gynecologic malignancies.
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  • Enlund, Mats, et al. (författare)
  • Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane
  • 2023
  • Ingår i: EClinicalMedicine. - : Elsevier. - 2589-5370. ; 60
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and perprotocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.
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  • Eschen, R, et al. (författare)
  • Carbon addition alters vegetation composition on ex-arable fields
  • 2007
  • Ingår i: Journal of Applied Ecology. - : Wiley. - 1365-2664 .- 0021-8901. ; 44:1, s. 95-104
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Recent changes in European agricultural policy have led to measures to reverse the loss of species-rich grasslands through the creation of new areas on ex-arable land. Ex-arable soils are often characterized by high inorganic nitrogen (N) levels, which lead to the rapid establishment of annual and fast-growing perennial species during the initial phase of habitat creation. The addition of carbon (C) to the soil has been suggested as a countermeasure to reduce plant-available N and alter competitive interactions among plant species. 2. To test the effect of C addition on habitat creation on ex-arable land, an experiment was set up on two recently abandoned fields in Switzerland and on two 6-year-old restoration sites in the UK. Carbon was added as a mixture of either sugar and sawdust or wood chips and sawdust during a period of 2 years. The effects of C addition on soil parameters and vegetation composition were assessed during the period of C additions and 1 year thereafter. 3. Soil nitrate concentrations were reduced at all sites within weeks of the first C addition, and remained low until cessation of the C additions. The overall effect of C addition on vegetation was a reduction in above-ground biomass and cover. At the Swiss sites, the addition of sugar and sawdust led to a relative increase in legume and forb cover and to a decrease in grass cover. The soil N availability, composition of soil micro-organisms and vegetation characteristics continued to be affected after cessation of C additions. 4. Synthesis and applications. The results suggest that C addition in grassland restoration is a useful management method to reduce N availability on ex-arable land. Carbon addition alters the vegetation composition by creating gaps in the vegetation that facilitates the establishment of late-seral plant species, and is most effective when started immediately after the abandonment of arable fields and applied over several years.
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36.
  • Gao, Boya, et al. (författare)
  • The ‘migratory connectivity’ concept, and its applicability to insect migrants
  • 2020
  • Ingår i: Movement Ecology. - : Springer Science and Business Media LLC. - 2051-3933. ; 8:1
  • Forskningsöversikt (refereegranskat)abstract
    • Migratory connectivity describes the degree of linkage between different parts of an animal’s migratory range due to the movement trajectories of individuals. High connectivity occurs when individuals from one particular part of the migratory range move almost exclusively to another localized part of the migratory range with little mixing with individuals from other regions. Conversely, low migratory connectivity describes the situation where individuals spread over a wide area during migration and experience a large degree of mixing with individuals from elsewhere. The migratory connectivity concept is frequently applied to vertebrate migrants (especially birds), and it is highly relevant to conservation and management of populations. However, it is rarely employed in the insect migration literature, largely because much less is known about the migration circuits of most migratory insects than is known about birds. In this review, we discuss the applicability of the migratory connectivity concept to long-range insect migrations. In contrast to birds, insect migration circuits typically comprise multigenerational movements of geographically unstructured (non-discrete) populations between broad latitudinal zones. Also, compared to the faster-flying birds, the lower degree of control over movement directions would also tend to reduce connectivity in many insect migrants. Nonetheless, after taking account of these differences, we argue that the migratory connectivity framework can still be applied to insects, and we go on to consider postulated levels of connectivity in some of the most intensively studied insect migrants. We conclude that a greater understanding of insect migratory connectivity would be of value for conserving threatened species and managing pests.
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37.
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38.
  • Gratzke, Christian, et al. (författare)
  • Cannabinor, a Selective Cannabinoid-2 Receptor Agonist, Improves Bladder Emptying in Rats With Partial Urethral Obstruction
  • 2011
  • Ingår i: JOURNAL OF UROLOGY. - : Elsevier Science B.V. Amsterdam. - 0022-5347 .- 1527-3792. ; 185:2, s. 731-736
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We studied the effects of chronic treatment with the novel selective cannabinoid 2 receptor agonist cannabinor (Procter andamp; Gamble Pharmaceuticals, Cincinnatti, Ohio) on bladder function in conscious rats with partial urethral obstruction and on the functional properties of isolated detrusor muscle. Materials and Methods: A total of 24 female Sprague-Dawley(R) rats with surgically created partial urethral obstruction received daily intraperitoneal injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks. Cystometry was done, the rats were sacrificed and the bladders were prepared for in vitro studies. Results: Mean +/- SEM bladder weight was 0.97 +/- 0.15 gm in controls and 0.53 +/- 0.08 gm in cannabinor treated rats (p andlt; 0.05). There was no difference between the groups in the mean micturition interval, or mean baseline, threshold, flow or maximum pressure. In controls and cannabinor treated rats mean post-void residual volume was 0.28 +/- 0.07 and 0.06 +/- 0.02 ml, mean micturition compliance was 0.032 +/- 0.006 and 0.069 +/- 0.016 ml/cm H2O, and mean bladder wall force at the start of flow was 950 +/- 280 and 1,647 +/- 325 mN/gm, respectively (each p andlt; 0.05). Nonvoiding contractions were significantly less frequent in cannabinor treated rats than in controls. We noted no difference in carbachol (Sigma(R)) half maximum concentration between the groups but the carbachol maximum response in detrusor strips from cannabinor treated rats was significantly higher than that in control strips. Conclusions: In rats with partial urethral obstruction treated daily for 14 days with cannabinor bladder weight was lower, the ability to empty the bladder was preserved and nonvoiding contraction frequency was low compared to those in controls. Detrusor preparations from cannabinor treated rats showed a higher response to nerve stimulation than those from controls. Selective cannabinoid 2 receptor activation may be a novel principle to enable improved bladder function after partial urethral obstruction.
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39.
  • Gratzke, Christian, et al. (författare)
  • Effects of cannabinor, a novel selective cannabinoid 2 receptor agonist, on bladder function in normal rats
  • 2010
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 57:6, s. 1093-1100
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established.OBJECTIVES: Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function.DESIGN, SETTING, AND PARTICIPANTS: Sprague Dawley rats were used. Distribution of CB2 receptors in sensory and cholinergic nerves of the detrusor was studied. Selectivity of cannabinor for human and rat CB receptors was evaluated. Effects of cannabinor on rat detrusor and micturition were investigated.MEASUREMENTS: Immunohistochemistry, radioligand binding, tritium outflow assays, organ bath studies of isolated bladder tissue, and cystometry in awake rats were used.RESULTS AND LIMITATIONS: CB2 receptor immunoreactivity was expressed in the urothelium and in sensory and cholinergic bladder nerves. Cannabinor exhibited similar binding at human and rat CB2 receptors and a 321-fold functional selectivity for the CB2 receptor versus the CB1 receptor. Cannabinor had no effect on isolated detrusor muscle function. In vivo, cannabinor 3.0mg/kg increased micturition intervals and volumes by 52% (p<0.05) and 96% (p<0.01), respectively, and increased threshold and flow pressures by 73% (p<0.01) and 49% (p<0.001), respectively. Cannabinor 0.3 or 1.0mg/kg or vehicle did not affect urodynamic parameters.CONCLUSIONS: Considering that CB2 receptors are localized on sensory nerves and on the urothelium and that cannabinor had effects on "afferent" urodynamic parameters, peripheral CB2 receptors may be involved in sensory functions of rat micturition. Effects of cannabinor on cholinergic nerve activity in normal bladder tissue appear to be limited.
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40.
  • Haddaway, Neal R., et al. (författare)
  • How does tillage intensity affect soil organic carbon? A systematic review
  • 2017
  • Ingår i: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 6:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: The loss of carbon (C) from agricultural soils has been, in part, attributed to tillage, a common practice providing a number of benefits to farmers. The promotion of less intensive tillage practices and no tillage (NT) (the absence of mechanical soil disturbance) aims to mitigate negative impacts on soil quality and to preserve soil organic carbon (SOC). Several reviews and meta-analyses have shown both beneficial and null effects on SOC due to no tillage relative to conventional tillage, hence there is a need for a comprehensive systematic review to answer the question: what is the impact of reduced tillage intensity on SOC? Methods: We systematically reviewed relevant research in boreoerate regions using, as a basis, evidence identified within a recently completed systematic map on the impacts of farming on SOC. We performed an update of the original searches to include studies published since the map search. We screened all evidence for relevance according to predetermined inclusion criteria. Studies were appraised and subject to data extraction. Meta-analyses were performed to investigate the impact of reducing tillage [from high (HT) to intermediate intensity (IT), HT to NT, and from IT to NT] for SOC concentration and SOC stock in the upper soil and at lower depths. Results: A total of 351 studies were included in the systematic review: 18% from an update of research published in the 2 years since the systematic map. SOC concentration was significantly higher in NT relative to both IT [1.18 g/kg ± 0.34 (SE)] and HT [2.09 g/kg ± 0.34 (SE)] in the upper soil layer (0-15 cm). IT was also found to be significant higher [1.30 g/kg ± 0.22 (SE)] in SOC concentration than HT for the upper soil layer (0-15 cm). At lower depths, only IT SOC compared with HT at 15-30 cm showed a significant difference; being 0.89 g/kg [± 0.20 (SE)] lower in intermediate intensity tillage. For stock data NT had significantly higher SOC stocks down to 30 cm than either HT [4.61 Mg/ha ± 1.95 (SE)] or IT [3.85 Mg/ha ± 1.64 (SE)]. No other comparisons were significant. Conclusions: The transition of tilled croplands to NT and conservation tillage has been credited with substantial potential to mitigate climate change via C storage. Based on our results, C stock increase under NT compared to HT was in the upper soil (0-30 cm) around 4.6 Mg/ha (0.78-8.43 Mg/ha, 95% CI) over ≥ 10 years, while no effect was detected in the full soil profile. The results support those from several previous studies and reviews that NT and IT increase SOC in the topsoil. Higher SOC stocks or concentrations in the upper soil not only promote a more productive soil with higher biological activity but also provide resilience to extreme weather conditions. The effect of tillage practices on total SOC stocks will be further evaluated in a forthcoming project accounting for soil bulk densities and crop yields. Our findings can hopefully be used to guide policies for sustainable management of agricultural soils.
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41.
  • Haddaway, Neal R., et al. (författare)
  • The benefits of systematic mapping to evidence-based environmental management
  • 2016
  • Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45:5, s. 613-620
  • Tidskriftsartikel (refereegranskat)abstract
    • Reviews of evidence are a vital means of summarising growing bodies of research. Systematic reviews (SRs) aim to reduce bias and increase reliability when summarising high priority and controversial topics. Similar to SRs, systematic maps (SMs) were developed in social sciences to reliably catalogue evidence on a specific subject. Rather than providing answers to specific questions of impacts, SMs aim to produce searchable databases of studies, along with detailed descriptive information. These maps (consisting of a report, a database, and sometimes a geographical information system) can prove highly useful for research, policy and practice communities, by providing assessments of knowledge gaps (subjects requiring additional research), knowledge gluts (subjects where full SR is possible), and patterns across the research literature that promote best practice and direct research resources towards the highest quality research. Here, we introduce SMs in detail using three recent case studies that demonstrate their utility for research and decision-making.
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42.
  • Haddaway, Neal R., et al. (författare)
  • What are the effects of agricultural management on soil organic carbon in boreo-temperate systems?
  • 2015
  • Ingår i: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 4
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Soils contain the largest stock of organic carbon (C) in terrestrial ecosystems and changes in soil C stocks may significantly affect atmospheric CO2. A significant part of soil C is present in cultivated soils that occupy about 35 % of the global land surface. Agricultural intensification has led to practices that may decrease soil organic carbon (SOC), and agricultural management has the potential to be a powerful tool for climate change mitigation and increased soil fertility through SOC sequestration. Here, we systematically map evidence relating to the impacts of agricultural management on SOC in arable systems of the warm temperate and snow climate zones (subset of temperate and continental climates: Köppen–Geiger Classification). Methods: Seventeen academic citation databases, 3 search engines and 25 organisational websites were searched for literature (academic and grey) using search strings translated into a range of languages relevant to the included geographical scope of the topic. Stakeholders were also contacted with requests for evidence. Bibliographic checking of 127 relevant reviews was undertaken to check for missing articles. Screening for relevance against predefined inclusion criteria was undertaken at title, abstract and full text levels according to a published protocol. All relevant studies were coded in a meta-database describing the citation, study settings, methods and quantitative data available (without extraction of the study findings). A basic critical appraisal of included studies was also performed. A geographical information system (GIS) presenting the map database on a physical, online map was also produced. Results: A total of 735 studies from 553 articles was included in the systematic map database. Studies investigated one or more of five broad categories of interventions: amendments (286 studies), crop rotations (238), fertilisers (307), tillage (306), and multiple interventions (55). Studies were identified from across the includible climate zones, with the notable underrepresentation from Russia. The majority of studies employed only point sampling of SOC, low levels of true spatial replication and moderate study periods (i.e. 10–20 years). Missing key methodological information was found in 28 % of studies. Conclusions: Long-term study sites identified in this map provide a useful addition to existing databases of longterm experiments (LTEs). The identification of knowledge gaps, such as studies from Russia, also identify a need for improved cataloguing or reporting of existing and on-going research. This systematic map database represents a useful resource for decision-makers wishing to identify knowledge gaps warranting further primary research, knowledge gluts warranting further secondary research, and deficiencies and best practice in research methodology. In addition to the systematic map database, we have also produced two further resources: (1) a database of LTE sites investigating agricultural management and SOC, and (2) a database of reviews and meta-analyses. To our knowledge, this is the first systematic review or map that utilises a GIS for presentation of an evidence base, which we believe substantially increases the utility of the map outputs.
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43.
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44.
  • Hayward, Alex, et al. (författare)
  • The genome sequence of the Brown Argus, Aricia agestis (Denis & Schiffermüller, 1775)
  • 2023
  • Ingår i: Wellcome Open Research. - 2398-502X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • We present genome assemblies from two male Aricia agestis specimens (the Brown Argus; Arthropoda; Insecta; Lepidoptera; Lycaenidae). The genome sequences are 435.3 and 437.4 megabases in span. Each assembly is scaffolded into 23 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genomes were assembled and are 15.47 and 15.45 kilobases in length. Gene annotation of these assemblies on Ensembl identified 12,688 and 12,654 protein coding genes.
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45.
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46.
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47.
  • Hedlund, Emma, et al. (författare)
  • Improved determination of the gas flow rate for UHV and leak metrology with laser refractometry
  • 2006
  • Ingår i: Measurement science and technology. - : IOP Publishing. - 0957-0233 .- 1361-6501. ; 17:10, s. 2767-2772
  • Tidskriftsartikel (refereegranskat)abstract
    • A system often used for vacuum metrology purposes in order to calibrate vacuum gauges in the UHV region and to calibrate gas leak rates is the throughput system, employing the continuous ( or dynamic) expansion method. An important component in such systems is the flowmeter, which has to deliver a pure and well-determined gas flow into the system. To determine the generated gas flow, a number of factors including the pressure inside the flowmeter have to be determined. However, it has turned out that the calibration uncertainty when measuring the pressure in the flowmeter gives a main contribution to the total uncertainty (of typically about 0.1%) for the generated flow, thereby limiting the accuracies of the generated vacuum pressure as well as gas leak rates in UHV metrology. A feasibility study is reported in this paper about the possibility of using laser refractometry to monitor dynamic gas density in situ in the flowmeter, as an alternative and possibly more accurate means of determining the generated gas flow, thereby potentially improving the calibration gas leak rates in the range 10(-8) - 10(-4) Pa m(3) s(-1).
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48.
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49.
  • Hedlund, G, et al. (författare)
  • Maximal interferon-gamma production and early synthesis of interleukin-2 by CD4+ CDw29- CD45R- p80- human T lymphocytes.
  • 1989
  • Ingår i: Immunology. - 0019-2805. ; 66:1, s. 49-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Functionally distinct subsets within the T-helper (CD4+) cell population have been described in man, rat and mouse. We have shown previously that the CD4+ 45R- human lymphocytes are producers of IL-2 within 24 hr of polyclonal stimulation and are the major interferon (IFN) producers. The mAbs 4B4 (CDw29) and Leu 8 (p80) are here used together with Leu-18 (CD45R) to characterize the subpopulations of the CD4+ human lymphocytes in more detail. The majority of the CD45R+ cells were CDw29- and the majority of the CDw29+ cells were CD45R-. Most of the CD45R+ cells (78%) were also p80+. A significant number of cells (12%) were CDw29- CD45R-. The predominant subpopulations were defined to be CDw29- CD45R+ p80+ (31%), CDw29+ CD45R- p80- (24%) and CDW29+ CD45R- p80+ (18%). Within the CD4+ CD45R- subpopulation different subsets vary in their capacities to produce IFN and to produce IL-2 within 24 hr after activation. CD4+ CDw29- CD45R- p80- T lymphocytes produced the largest quantities of IFN and IL-2.
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50.
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