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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Harvey, K, et al.
(författare)
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The GDP-GTP exchange factor collybistin: An essential determinant of neuronal gephyrin clustering
- 2004
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 24:25, s. 5816-5826
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Tidskriftsartikel (refereegranskat)abstract
- Glycine receptors (GlyRs) and specific subtypes of GABA(A) receptors are clustered at synapses by the multidomain protein gephyrin, which in turn is translocated to the cell membrane by the GDP-GTP exchange factor collybistin. We report the characterization of several new variants of collybistin, which are created by alternative splicing of exons encoding an N-terminal src homology 3 (SH3) domain and three alternate C termini (CB1, CB2, and CB3). The presence of the SH3 domain negatively regulates the ability of collybistin to translocate gephyrin to submembrane microaggregates in transfected mammalian cells. Because the majority of native collybistin isoforms appear to harbor the SH3 domain, this suggests that collybistin activity may be regulated by protein-protein interactions at the SH3 domain. We localized the binding sites for collybistin and the GlyR beta subunit to the C-terminal MoeA homology domain of gephyrin and show that multimerization of this domain is required for collybistin-gephyrin and GlyR-gephyrin interactions. We also demonstrate that gephyrin clustering in recombinant systems and cultured neurons requires both collybistin-gephyrin interactions and an intact collybistin pleckstrin homology domain. The vital importance of collybistin for inhibitory synaptogenesis is underlined by the discovery of a mutation (G55A) in exon 2 of the human collybistin gene (ARHGEF9) in a patient with clinical symptoms of both hyperekplexia and epilepsy. The clinical manifestation of this collybistin missense mutation may result, at least in part, from mislocalization of gephyrin and a major GABA(A) receptor subtype.
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| 13. |
- Rees, CA, et al.
(författare)
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Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries
- 2022
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2–59 months at risk of hospitalised pneumonia-related mortality across various settings.MethodsWe used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool.ResultsA total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84).ConclusionsThe PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.
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| 15. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 17. |
- Spicer, RA, et al.
(författare)
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Palaeoenvironment and ecology of the middle Cretaceous Grebenka flora of northeastern Asia
- 2002
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Ingår i: Palaeogeography, Palaeoclimatology, Palaeoecology. - 1872-616X. ; 184:1-2, s. 65-105
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Tidskriftsartikel (refereegranskat)abstract
- The Grebenka flora, from the main exposure of the Albian-Cenomanian Krivorechenskaya Formation in northeastern Russia, represents a range of plant communities from pioneer to mature forest that grew close to the mid-Cretaceous North Pole (> 72degreesN). The diversity of this flora is dominated by angiosperms followed by conifers, ferns and other plant groups. The age is constrained by Ar-40/Ar-39 analyses of associated volcaniclastics (similar to 96.5 Ma), coupled with biostratigraphic correlation of the plant-bearing non-marine beds with marine units of the Krivorechenskaya Formation and the overlying Dugovskaya Formation. Limited palaeosol development and pronounced episodic floodplain aggradation indicate that the 100-m-thick plant-bearing volcaniclastic floodplain succession was deposited rapidly, resulting in excellent trapping and preservation of the plant communities, but dilution of the palynoflora. Analysis of the megaflora (> 100 foliage taxa, plus woods and fructifications) provides a 'snapshot' of the mid-Cretaceous climate, and offers reliable quantitative climatic signals of conditions near the mid-Cretaceous North Pole. Multivariate analysis of leaf physiognomy (Climate Leaf Analysis Multivariate Program) on the whole flora suggests that the plants experienced a mean annual temperature of 13.0 +/- 1.8degreesC and a cold month mean temperature of 5.5 +/- 3.3degreesC. However, analyses of individual florules yield slightly different results that help constrain the uncertainties inherent in such an approach. These and other foliar physiognomic data are compared across the Arctic.
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