| 1. |
- Környei, Bálint S., et al.
(författare)
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Cerebral microbleeds may be less detectable by susceptibility weighted imaging MRI from 24 to 72 hours after traumatic brain injury
- 2021
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A former rodent study showed that cerebral traumatic microbleeds (TMBs) may temporarily become invisible shortly after injury when detected by susceptibility weighted imaging (SWI). The present study aims to validate this phenomenon in human SWI.Methods: In this retrospective study, 46 traumatic brain injury (TBI) patients in various forms of severity were included and willingly complied with our strict selection criteria. Clinical parameters potentially affecting TMB count, Rotterdam and Marshall CT score, Mayo Clinic Classification, contusion number, and total volume were registered. The precise time between trauma and MRI [5 h 19 min to 141 h 54 min, including SWI and fluid-attenuated inversion recovery (FLAIR)] was individually recorded; TMB and FLAIR lesion counts were assessed. Four groups were created based on elapsed time between the trauma and MRI: 0-24, 24-48, 48-72, and >72 h. Kruskal-Wallis, ANOVA, Chi-square, and Fisher's exact tests were used to reveal differences among the groups within clinical and imaging parameters; statistical power was calculated retrospectively for each comparison.Results: The Kruskal-Wallis ANOVA with Conover post hoc analysis showed significant (p = 0.01; 1-β > 0.9) median TMB number differences in the subacute period: 0-24 h = 4.00 (n = 11); 24-48 h = 1 (n = 14); 48-72 h = 1 (n = 11); and 72 h ≤ 7.5 (n = 10). Neither clinical parameters nor FLAIR lesions depicted significant differences among the groups.Conclusion: Our results demonstrate that TMBs on SWI MRI may temporarily become less detectable at 24-72 h following TBI.
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| 2. |
- Petersen, Julian, et al.
(författare)
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A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.
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| 3. |
- Szucs, Edina, et al.
(författare)
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Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives
- 2020
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Ingår i: European Journal of Medicinal Chemistry. - : ELSEVIER. - 0223-5234 .- 1768-3254. ; 191
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Tidskriftsartikel (refereegranskat)abstract
- Morphine and its derivatives play inevitably important role in the m-opioid receptor (MOR) targeted antinociception. A structure-activity relationship study is presented for novel and known orvinol and thevinol derivatives with varying 3-O, 6-O, 17-N and 20-alkyl substitutions starting from agonists, antagonists and partial agonists. In vitro competition binding experiments with [H-3]DAMGO showed low subnanomolar affinity to MOR. Generally, 6-O-demethylation increased the affinity toward MOR and decreased the efficacy changing the pharmacological profile in some cases. In vivo tests in osteoarthritis inflammation model showed significant antiallodynic effects of thevinol derivatives while orvinol derivatives did not. The pharmacological character was modelled by computational docking to both active and inactive state models of MOR. Docking energy difference for the two states separates agonists and antagonists well while partial agonists overlapped with them. An interaction pattern of the ligands, involving the interacting receptor atoms, showed more efficient separation of the pharmacological profiles. In rats, thevinol derivatives showed antiallodynic effect in vivo. The orvinol derivatives, except for 6-O-desmethyl-dihydroetorfin (2c), did not show antiallodynic effect.
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| 4. |
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| 5. |
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| 6. |
- Góger, Szabolcs, et al.
(författare)
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Flame Inhibition Chemistry : Rate Coefficients of the Reactions of HBr with CH3 and OH Radicals at High Temperatures Determined by Quasiclassical Trajectory Calculations
- 2018
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Ingår i: Energy & Fuels. - : American Chemical Society (ACS). - 0887-0624 .- 1520-5029. ; 32:10, s. 10100-10105
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Tidskriftsartikel (refereegranskat)abstract
- Reactions of HBr with radicals are involved in atmospheric chemistry and in the mechanism of operation of bromine-containing flame retardants. The rate coefficients for two such reactions, HBr + OH and HBr + CH3, are available from earlier experiments at near or below room temperature, relevant for atmospheric chemistry, and in this domain, the activation energy for both has been found to be negative. However, no experimental data are available at combustion temperatures. In this work, to provide reliable data needed for modeling the action of brominated flame suppressants, we used the quasiclassical trajectory (QCT) method in combination with high-level ab initio potential energy surfaces to evaluate the rate coefficients of the two title reactions at combustion temperatures. The QCT calculations have been validated by reproducing the experimental rate coefficients at room temperature. At temperatures between 600 and 3200 K, the QCT rate coefficients display positive activation energies. We recommend the following extended Arrhenius expressions to describe the temperature dependence of the thermal rate coefficients: k6 = (9.86 ± 2.38) × 10–16T(1.23±0.03) exp[(5.93 ± 0.33) kJ mol–1/RT] cm3 molecule–1 s–1 for the HBr + OH → H2O + Br reaction, and k–2 = (4.06 ± 2.72) × 10–18T(1.83±0.08) exp[(7.53 ± 0.18) kJ mol–1/RT] cm3 molecule–1 s–1 for the HBr + CH3 → CH4 + Br reaction. The latter is in very good agreement with the formula proposed by Burgess et al. [Burgess, D. R., Jr.; Babushok, V. I.; Linteris, G. T.; Manion, J. A. A Chemical Kinetic Mechanism for 2-Bromo-3,3,3-trifluoropropene (2-BTP) Flame Inhibition. Int. J. Chem. Kinet. 2015, 47, 533−619, DOI: 10.1002/kin.20923]. The conventional transition state theory has been tested against the rate data obtained by the QCT method and was found to overestimate not only the rate coefficients but also the activation energies
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| 7. |
- Ledri, Marco, et al.
(författare)
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Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.
- 2012
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 36:1, s. 1971-1983
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Tidskriftsartikel (refereegranskat)abstract
- Cholecystokinin (CCK-) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine-tuning devices of hippocampal gamma-frequency (30-90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK-basket cells may play an important role in regulation of hyper-excitability and seizures in the hippocampus. In normal conditions, the endogenous excitability regulator neuropeptide Y (NPY) has been shown to modulate afferent inputs onto dentate gyrus CCK-basket cells, providing a possible novel mechanism for excitability control in the hippocampus. Using GAD65-GFP mice for CCK-basket cell identification, and whole-cell patch-clamp recordings, we explored whether the effect of NPY on afferent synapses to CCK-basket cells is modified in the hyper-excitable dentate gyrus. To induce a hyper-excitable state, recurrent seizures were evoked by electrical stimulation of the hippocampus using the well-characterized rapid kindling protocol. The frequency of spontaneous and miniature excitatory and inhibitory post-synaptic currents recorded in CCK-basket cells was decreased by NPY. The excitatory post-synaptic currents evoked in CCK-basket cells by optogenetic activation of principal neurons were also decreased in amplitude. Interestingly, we observed an increased proportion of spontaneous inhibitory post-synaptic currents with slower rise times, indicating that NPY may inhibit gamma aminobutyric acid release preferentially in peri-somatic synapses. These findings indicate that increased levels and release of NPY observed after seizures can modulate afferent inputs to CCK-basket cells, and therefore alter their impact on the oscillatory network activity and excitability in the hippocampus.
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| 8. |
- Ledri, Marco, et al.
(författare)
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Tuning afferent synapses of hippocampal interneurons by neuropeptide Y.
- 2011
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Ingår i: Hippocampus. - : Wiley. - 1050-9631. ; 21, s. 198-211
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Tidskriftsartikel (refereegranskat)abstract
- Cholecystokinin (CCK)-expressing basket cells encompass a subclass of inhibitory GABAergic interneurons that regulate memory-forming oscillatory network activity of the hippocampal formation in accordance to the emotional and motivational state of the animal, conveyed onto these cells by respective extrahippocampal afferents. Various excitatory and inhibitory afferent and efferent synapses of the hippocampal CCK basket cells express serotoninergic, cholinergic, cannabinoid, and benzodiazepine sensitive receptors, all contributing to their functional plasticity. We explored whether CCK basket cells are modulated by neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits hippocampal excitability and has significant effect on its memory function. Here, using GAD65-GFP transgenic mice for prospective identification of CCK basket cells and whole-cell patch-clamp recordings, we show for the first time that excitatory and inhibitory inputs onto CCK basket cells in the dentate gyrus of the hippocampus are modulated by NPY through activation of NPY Y2 receptors. The frequency of spontaneous and miniature EPSCs, as well as the amplitudes of stimulation-evoked EPSCs were decreased. Similarly, the frequency of both spontaneous and miniature IPSCs, and the amplitudes of stimulation-evoked IPSCs were decreased after NPY application. Most of the effects of NPY could be attributed to a presynaptic site of action. Our data provide the first evidence that the excitatory and inhibitory inputs onto the CCK basket cells could be modulated by local levels of NPY, and may change the way these cells process extrahippocampal afferent information, influencing hippocampal function and its network excitability during normal and pathological oscillatory activities. (c) 2009 Wiley-Liss, Inc.
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| 9. |
- Malenczyk, Katarzyna, et al.
(författare)
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A TRPV1-to-secretagogin regulatory axis controls pancreatic β-cell survival by modulating protein turnover
- 2017
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Ingår i: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 36:14, s. 1993-2176
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Tidskriftsartikel (refereegranskat)abstract
- Ca2+-sensor proteins are generally implicated in insulin release through SNARE interactions. Here, secretagogin, whose expression in human pancreatic islets correlates with their insulin content and the incidence of type 2 diabetes, is shown to orchestrate an unexpectedly distinct mechanism. Single-cell RNA-seq reveals retained expression of the TRP family members in β-cells from diabetic donors. Amongst these, pharmacological probing identifies Ca2+-permeable transient receptor potential vanilloid type 1 channels (TRPV1) as potent inducers of secretagogin expression through recruitment of Sp1 transcription factors. Accordingly, agonist stimulation of TRPV1s fails to rescue insulin release from pancreatic islets of glucose intolerant secretagogin knock-out(-/-) mice. However, instead of merely impinging on the SNARE machinery, reduced insulin availability in secretagogin-/- mice is due to β-cell loss, which is underpinned by the collapse of protein folding and deregulation of secretagogin-dependent USP9X deubiquitinase activity. Therefore, and considering the desensitization of TRPV1s in diabetic pancreata, a TRPV1-to-secretagogin regulatory axis seems critical to maintain the structural integrity and signal competence of β-cells.
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| 10. |
- Mannelquist, Anders, et al.
(författare)
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Near-field optical microscopy with a vibrating probe in aqueous solution
- 2001
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 78:14, s. 2076-2078
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Tidskriftsartikel (refereegranskat)abstract
- We show that with an appropriately configured scanning quartz pipette coated with aluminum, a near-field scanning optical microscope (NSOM) can be constructed to operate in aqueous solution for applications in biology. Many of the technical limitations associated with a scanning pipette were circumvented by introducing a small modulation of the distance between the pipette and the sample. We show that this ac method allows the pipette to be positioned very close to the sample surface and is robust in obtaining reproducible NSOM images in solution. This approach is also compatible with fluorescence imaging and fluorescence resonance energy transfer, and should further facilitate the use of NSOM in various areas of cell biology where high resolution is considered to be critical.
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