| 111281. |
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| 111282. |
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| 111283. |
- Kögl, Matthias, et al.
(författare)
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Single Shot SLIPI LIF/Mie Ratio for Droplet Sizing in DISI-Sprays
- 2016
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Ingår i: ILASS – Europe 2016, 27th Annual Conference on Liquid Atomization and Spray Systems, 4-7 September 2016.
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Konferensbidrag (refereegranskat)abstract
- This paper reports on the first realization of two-phase SLIPI (Structured Laser Illumination Planar Imaging) in combination with LIF/Mie ratio imaging for a single shot mapping of relative SMD (Sauter Mean Diameter) in a transient fuel spray. The technique is applied to a non-combusting multi-jet DISI (direct-injection spark-ignition) spray of ethanol fuel injected into an optically accessible constant volume chamber. The organic dye Eosin is added to the fuel as a laser-induced fluorescence (LIF) tracer when illuminated by the 532nm laser sheet. It is found that SLIPI produces more reliable relative SMD distributions in comparison to the conventional LIF/Mie-approach. Multiple scattered light is suppressed by the SLIPI technique and the background spray plumes and artifacts behind the illuminated plane are successfully suppressed. The single-shot SLIPI images give a clear insight into the highly turbulent liquid spray structure and provide reliable information on the spatial droplet distribution.
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| 111284. |
- Kögler, T., et al.
(författare)
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Fast-neutron-induced fission cross section of Pu 242 measured at the neutron time-of-flight facility nELBE
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 99:2
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Tidskriftsartikel (refereegranskat)abstract
- The fast-neutron-induced fission cross section of Pu242 was measured at the neutron time-of-flight facility nELBE. A parallel-plate fission ionization chamber with novel, homogeneous, large-area Pu242 deposits on Si-wafer backings was used to determine this quantity relative to the IAEA neutron cross-section standard U235(n,f) in the energy range of 0.5 to 10 MeV. The number of target nuclei was determined from the measured spontaneous fission rate of Pu242. This helps to reduce the influence of the fission fragment detection efficiency on the cross section. Neutron transport simulations performed with geant4, mcnp6, and fluka2011 are used to correct the cross-section data for neutron scattering. In the reported energy range the systematic uncertainty is below 2.7% and on average the statistical uncertainty is 4.9%. The determined results show an agreement within 0.67(16)% to recently published data and a good accordance to current evaluated data sets.
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| 111285. |
- Köhler, Aleksandra, et al.
(författare)
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Genome-wide association study on differentiated thyroid cancer.
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:10, s. 1674-1681
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Tidskriftsartikel (refereegranskat)abstract
- Context:Genome-wide association studies (GWASs) of differentiated thyroid cancer (DTC) have identified associations with polymorphisms at 2q35 (DIRC3), 8p12 (NRG1), 9q22.33 (FOXE1) and 14q13.2 (NKX2-1). However, most of the inherited genetic risk factors of DTC remain to be discovered.Objective:Our objective was to identify additional common DTC susceptibility loci.Design:We conducted a GWAS in a high-incidence Italian population of 690 cases and 497 controls and followed up the most significant polymorphisms in two additional Italian series and in three low-incidence populations totaling 2,958 cases and 3,727 controls.Results:After excluding the most robust previously identified locus (9q22.33), the strongest association was shown by rs6759952 confirming the recently published association in DIRC3 (OR = 1.21, P = 6.4 × 10(-10), GWAS and all replications combined). Additionally, in the combined analysis of the Italian series, suggestive associations were attained with rs10238549 and rs7800391 in IMMP2L (OR = 1.27, P = 4.1 × 10(-6) and OR = 1.25, P = 5.7 × 10(-6)), rs7617304 in RARRES1 (OR =1.25, P = 4.6 × 10(-5)) and rs10781500 in SNAPC4/CARD9 (OR = 1.23, P = 3.5 × 10(-5)).Conclusions:Our findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to DTC. Further studies are needed to determine the role of the identified polymorphisms in the development of DTC and their possible use in the clinical practice.
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| 111286. |
- Köhler, Anna, et al.
(författare)
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New specific HSP47 functions in collagen subfamily chaperoning
- 2020
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Ingår i: FASEB Journal. - 0892-6638. ; 34:9, s. 12040-12052
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Tidskriftsartikel (refereegranskat)abstract
- Although collagens are the most abundant proteins implicated in various disease pathways, essential mechanisms required for their proper folding and assembly are poorly understood. Heat-shock protein 47 (HSP47), an ER-resident chaperone, was mainly reported to fulfill key functions in folding and secretion of fibrillar collagens by stabilizing pro-collagen triple-helices. In this study, we demonstrate unique functions of HSP47 for different collagen subfamilies. Our results show that HSP47 binds to the N-terminal region of procollagen I and is essential for its secretion. However, HSP47 ablation does not majorly impact collagen VI secretion, but its lateral assembly. Moreover, specific ablation of Hsp47 in murine keratinocytes revealed a new role for the transmembrane collagen XVII triple-helix formation. Incompletely folded collagen XVII C-termini protruding from isolated HSP47 null keratinocyte membrane vesicles could be fully restored upon the application of recombinant HSP47. Thus, our study expands the current view regarding the client repertoire and function of HSP47, as well as emphasizes its importance for transmembrane collagen folding.
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| 111287. |
- Köhler, Camilla, et al.
(författare)
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A folding variant of human alpha-lactalbumin induces mitochondrial permeability transition in isolated mitochondria
- 2001
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956. ; 268:1, s. 186-191
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Tidskriftsartikel (refereegranskat)abstract
- A human milk fraction containing multimeric alpha-lactalbumin (MAL) is able to kill cells via apoptosis. MAL is a protein complex of a folding variant of alpha-lactalbumin and lipids. Previous results have shown that upon treatment of transformed cells, MAL localizes to the mitochondria and cytochrome c is released into the cytosol. This is followed by activation of the caspase cascade. In this study, we further investigated the involvement of mitochondria in apoptosis induced by the folding variant of alpha-lactalbumin. Addition of MAL to isolated rat liver mitochondria induced a loss of the mitochondrial membrane potential (Delta Psi(m)), mitochondrial swelling and the release of cytochrome c. These changes were Ca(2+)-dependent and were prevented by cyclosporin A, an inhibitor of mitochondrial permeability transition. MAL also increased the rate of state 4 respiration in isolated mitochondria by exerting an uncoupling effect. This effect was due to the presence of fatty acids in the MAL complex because it was abolished completely by BSA. BSA delayed, but failed to prevent, mitochondrial swelling as well as dissipation of Delta Psi(m), indicating that the fatty acid content of MAL facilitated, rather than caused, these effects. Similar results were obtained with HAMLET (human alpha-lactalbumin made lethal to tumour cells), which is native alpha-lactalbumin converted in vitro to the apoptosis-inducing folding variant of the protein in complex with oleic acid. Our findings demonstrate that a folding variant of alpha-lactalbumin induces mitochondrial permeability transition with subsequent cytochrome c release, which in transformed cells may lead to activation of the caspase cascade and apoptotic death.
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| 111288. |
- Köhler, Christian, et al.
(författare)
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Backbone 1H, 13C, and 15N resonance assignments of the ligand binding domain of the human wildtype glucocorticoid receptor and the F602S mutant variant
- 2018
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Ingår i: Biomolecular NMR Assignments. - : Springer Science and Business Media LLC. - 1874-2718 .- 1874-270X. ; 12:2, s. 263-268
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Tidskriftsartikel (refereegranskat)abstract
- The glucocorticoid receptor (GR) is a nuclear hormone receptor that regulates key genes controlling development, metabolism, and the immune response. GR agonists are efficacious for treatment of inflammatory, allergic, and immunological disorders. Steroid hormone binding to the ligand-binding domain (LBD) of GR is known to change the structural and dynamical properties of the receptor, which in turn control its interactions with DNA and various co-regulators and drive the pharmacological response. Previous biophysical studies of the GR LBD have required the use of mutant forms to overcome issues with limited protein stability and high aggregation propensity. However, these mutant variants are known to also influence the functional response of the receptor. Here we report a successful protocol for protein expression, purification, and NMR characterization of the wildtype human GR LBD. We achieved chemical shift assignments for 90% of the LBD backbone resonances, with 216 out of 240 non-proline residues assigned in the 1H–15N TROSY spectrum. These advancements form the basis for future investigations of allosteric effects in GR signaling.
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| 111289. |
- Köhler, Christian, et al.
(författare)
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Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:29
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Tidskriftsartikel (refereegranskat)abstract
- Allosteric communication within proteins is a hallmark of biochemical signaling, but the dynamic transmission pathways remain poorly characterized. We combined NMR spectroscopy and surface plasmon resonance to reveal these pathways and quantify their energetics in the glucocorticoid receptor, a transcriptional regulator controlling development, metabolism, and immune response. Our results delineate a dynamic communication network of residues linking the ligand-binding pocket to the activation function-2 interface, where helix 12, a switch for transcriptional activation, exhibits ligand- and coregulator-dependent dynamics coupled to graded activation. The allosteric free energy responds to variations in ligand structure: subtle changes gradually tune allostery while preserving the transmission pathway, whereas substitution of the entire pharmacophore leads to divergent allosteric control by apparently rewiring the communication network. Our results provide key insights that should aid in the design of mechanistically differentiated ligands.
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| 111290. |
- Köhler, Jan, et al.
(författare)
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Long-term effects of reflux nephropathy on blood pressure and renal function in adults.
- 2003
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Ingår i: Nephron Clinical Practice. - : S. Karger AG. - 1660-2110. ; 93:1, s. 35-46
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Tidskriftsartikel (refereegranskat)abstract
- <i>Aims:</i> We investigated whether the grade of renal damage assessed by urography in adult patients with vesicoureteral reflux can be used to identify patients at risk of developing hypertension and/or deterioration of renal function. In addition, maternal and fetal outcome of pregnancy was studied. <i>Methods:</i> Vesicoureteral reflux was diagnosed at a median age of 27 years (range 16–60) in 115 patients (98 women). Excluding patients subjected to nephrectomy or heminephrectomy after inclusion (n = 12), 88 patients had renal damage at inclusion urography and a median follow-up time of 16 years. The median follow-up time was 18 years in 15 patients without renal damage. Grading of renal damage was performed and blood pressure, serum creatinine concentration and albuminuria were measured. Hypertension was considered to be present if the systolic blood pressure was ≧140 mm Hg and/or the diastolic blood pressure was ≧90 mm Hg. It was classified as mild (<180 mm Hg systolic and <105 mm Hg diastolic), or moderate to severe (≧180 mm Hg systolic and/or ≧105 mm Hg diastolic). Renal function was classified as stable or deteriorating. <i>Results:</i> There was no significant difference in the frequency of hypertension among those with (52%) or without (33%) renal damage, but moderate to severe hypertension (16 patients) was only seen in patients with renal damage. Median systolic and diastolic blood pressure were higher in patients with than in those without renal damage. Malignant hypertension developed in 4 patients, all had extensive renal damage. Deterioration of renal function occurred in 25 patients, 1 with unilateral and 24 with extensive renal damage (bilateral or in a solitary kidney). This was associated with a high frequency of hypertension (92%) and albuminuria (88%). Sixteen patients developed end-stage renal disease. A total of 242 pregnancies occurred in 89 of the 98 women. Preeclampsia occurred in 16 (18%) women. <i>Conclusion:</i> Hypertension in adult patients with reflux nephropathy occurs with any grade of renal damage, whereas deterioration of renal function was strongly associated with extensive bilateral renal damage or damage in a solitary kidney.
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