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- Gherardi, E, et al.
(författare)
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Structural basis of hepatocyte growth factor/scatter factor and MET signalling
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 103:11, s. 4046-4051
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Tidskriftsartikel (refereegranskat)abstract
- The polypeptide growth factor, hepatocyte growth factor/scatter factor (HGF/SF), shares the multidomain structure and proteolytic mechanism of activation of plasminogen and other complex serine proteinases. HGF/SF, however, has no enzymatic activity. Instead, it controls the growth, morphogenesis, or migration of epithelial, endothelial, and muscle progenitor cells through the receptor tyrosine kinase MET. Using small-angle x-ray scattering and cryo-electron microscopy, we show that conversion of pro(single-chain)HGF/SF into the active two-chain form is associated with a major structural transition from a compact, closed conformation to an elongated, open one. We also report the structure of a complex between two-chain HGF/SF and the MET ectodomain (MET928) with 1:1 stoichiometry in which the N-terminal and first kringle domain of HGF/SF contact the face of the seven-blade β-propeller domain of MET harboring the loops connecting the β-strands b–c and d–a, whereas the C-terminal serine proteinase homology domain binds the opposite “b” face. Finally, we describe a complex with 2:2 stoichiometry between two-chain HGF/SF and a truncated form of the MET ectodomain (MET567), which is assembled around the dimerization interface seen in the crystal structure of the NK1 fragment of HGF/SF and displays the features of a functional, signaling unit. The study shows how the proteolytic mechanism of activation of the complex proteinases has been adapted to cell signaling in vertebrate organisms, offers a description of monomeric and dimeric ligand-receptor complexes, and provides a foundation to the structural basis of HGF/SF-MET signaling.
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- Klaile, E, et al.
(författare)
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The CEACAM1 N-terminal Ig domain mediates cis- and trans-binding and is essential for allosteric rearrangements of CEACAM1 microclusters
- 2009
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Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 187:4, s. 553-567
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Tidskriftsartikel (refereegranskat)abstract
- Cell adhesion molecules (CAMs) sense the extracellular microenvironment and transmit signals to the intracellular compartment. In this investigation, we addressed the mechanism of signal generation by ectodomains of single-pass transmembrane homophilic CAMs. We analyzed the structure and homophilic interactions of carcinoembryonic antigen (CEA)–related CAM 1 (CEACAM1), which regulates cell proliferation, apoptosis, motility, morphogenesis, and microbial responses. Soluble and membrane-attached CEACAM1 ectodomains were investigated by surface plasmon resonance–based biosensor analysis, molecular electron tomography, and chemical cross-linking. The CEACAM1 ectodomain, which is composed of four glycosylated immunoglobulin-like (Ig) domains, is highly flexible and participates in both antiparallel (trans) and parallel (cis) homophilic binding. Membrane-attached CEACAM1 ectodomains form microclusters in which all four Ig domains participate. Trans-binding between the N-terminal Ig domains increases formation of CEACAM1 cis-dimers and changes CEACAM1 interactions within the microclusters. These data suggest that CEACAM1 transmembrane signaling is initiated by adhesion-regulated changes of cis-interactions that are transmitted to the inner phase of the plasma membrane.
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- Nygren, Gudrun, 1957, et al.
(författare)
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The Swedish version of the Diagnostic Interview for Social and Communication Disorders (DISCO-10). Psychometric properties.
- 2009
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Ingår i: Journal of Autism and Developmental Disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 39:5, s. 730-741
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Tidskriftsartikel (refereegranskat)abstract
- Psychometric properties of the Diagnostic Interview for Social and Communication Disorders schedule (DISCO) have only been studied in the UK. The authorised Swedish translation of the tenth version of the DISCO (DISCO-10) was used in interviews with close relatives of 91 Swedish patients referred for neuropsychiatrical assessment. Validity analysis compared DISCO-10-algorithm diagnoses with clinical diagnoses and with Autism Diagnostic Interview Revised (ADI-R) algorithm diagnoses in 57 cases. Good-excellent inter-rater reliability was demonstrated in 40 cases of children and adults. The criterion validity was excellent when compared with clinical diagnoses and an investigator-based diagnostic interview. The DISCO-10 has good psychometric properties. Advantages over the ADI-R include valuable information of the broader autism phenotype and co-existing problems for clinical practice and research.
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- Skoglund, L, et al.
(författare)
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Qigong reduces stress in computer operators
- 2007
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Ingår i: complementary therapies in clinical practice. - : Elsevier BV. - 1744-3881. ; 13:2, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- Summary Chinese research indicates that the Qigong method reduces psychosomatic and physical symptoms through an effect on the sympathetic nervous system. Objectives The aim was to investigate the effects of Qigong on stress among computer operators. Design Ten women were included in a Qigong group and an equal number in a control group. Heart rate, blood pressure, and finger temperature were measured at the beginning and at the end of the working day during 5 weeks. twenty four-hours urine samples were collected in the first and last weeks to measure catecholamine excretion in urine. Participants kept a daily record of psychological measures of strain and weekly measures of stress levels. Results and conclusions Qigong reduced noradrenaline excretion in urine (p<0.05), and influenced the heart rate and temperature, indicating reduced activity of the sympathetic nervous system. Moreover, Qigong reduced low-back symptoms (p<0.05). In conclusion, Qigong exercise may reduce stress at computerised work.
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