TY - JOUR AU - Dreier, Jens P. AU - Winkler, Maren K. L. AU - Major, Sebastian AU - Horst, Viktor AU - Lublinsky, Svetlana AU - Kola, Vasilis AU - Lemale, Coline L. AU - Kang, Eun-Jeung AU - Maslarova, Anna AU - Salur, Irmak AU - Lückl, János AU - Platz, Johannes AU - Jorks, Devi AU - Oliveira-Ferreira, Ana I. AU - Schoknecht, Karl AU - Reiffurth, Clemens AU - Milakara, Denny AU - Wiesenthal, Dirk AU - Hecht, Nils AU - Dengler, Nora F. AU - Liotta, Agustin AU - Wolf, Stefan AU - Kowoll, Christina M. AU - Schulte, André P. AU - Santos, Edgar AU - Güresir, Erdem AU - Unterberg, Andreas W. AU - Sarrafzadeh, Asita AU - Sakowitz, Oliver W. AU - Vatter, Hartmut AU - Reiner, Michael AU - Brinker, Gerrit AU - Dohmen, Christian AU - Shelef, Ilan AU - Bohner, Georg AU - Scheel, Michael AU - Vajkoczy, Peter AU - Hartings, Jed A. AU - Friedman, Alon AU - Martus, Peter AU - Woitzik, Johannes TI - Spreading depolarizations in ischaemia after subarachnoid haemorrhage, a diagnostic phase III study JF - BRAIN J2 - BRAIN VL - 145 PY - 2022 IS - 4 SP - 1264 EP - 1284 PG - 21 SN - 0006-8950 DO - 10.1093/brain/awab457 UR - https://m2.mtmt.hu/api/publication/32781700 ID - 32781700 AB - Focal brain damage after aneurysmal subarachnoid haemorrhage predominantly results from intracerebral haemorrhage, and early and delayed cerebral ischaemia. The prospective, observational, multicentre, cohort, diagnostic phase III trial, DISCHARGE-1, primarily investigated whether the peak total spreading depolarization-induced depression duration of a recording day during delayed neuromonitoring (delayed depression duration) indicates delayed ipsilateral infarction. Consecutive patients (n = 205) who required neurosurgery were enrolled in six university hospitals from September 2009 to April 2018. Subdural electrodes for electrocorticography were implanted. Participants were excluded on the basis of exclusion criteria, technical problems in data quality, missing neuroimages or patient withdrawal (n = 25). Evaluators were blinded to other measures. Longitudinal MRI, and CT studies if clinically indicated, revealed that 162/180 patients developed focal brain damage during the first 2 weeks. During 4.5 years of cumulative recording, 6777 spreading depolarizations occurred in 161/180 patients and 238 electrographic seizures in 14/180. Ten patients died early; 90/170 developed delayed infarction ipsilateral to the electrodes. Primary objective was to investigate whether a 60-min delayed depression duration cut-off in a 24-h window predicts delayed infarction with >0.60 sensitivity and >0.80 specificity, and to estimate a new cut-off. The 60-min cut-off was too short. Sensitivity was sufficient [= 0.76 (95% confidence interval: 0.65-0.84), P = 0.0014] but specificity was 0.59 (0.47-0.70), i.e. <0.80 (P < 0.0001). Nevertheless, the area under the receiver operating characteristic (AUROC) curve of delayed depression duration was 0.76 (0.69-0.83, P < 0.0001) for delayed infarction and 0.88 (0.81-0.94, P < 0.0001) for delayed ischaemia (reversible delayed neurological deficit or infarction). In secondary analysis, a new 180-min cut-off indicated delayed infarction with a targeted 0.62 sensitivity and 0.83 specificity. In awake patients, the AUROC curve of delayed depression duration was 0.84 (0.70-0.97, P = 0.001) and the prespecified 60-min cut-off showed 0.71 sensitivity and 0.82 specificity for reversible neurological deficits. In multivariate analysis, delayed depression duration (beta = 0.474, P < 0.001), delayed median Glasgow Coma Score (beta = -0.201, P = 0.005) and peak transcranial Doppler (beta = 0.169, P = 0.016) explained 35% of variance in delayed infarction. Another key finding was that spreading depolarization-variables were included in every multiple regression model of early, delayed and total brain damage, patient outcome and death, strongly suggesting that they are an independent biomarker of progressive brain injury. While the 60-min cut-off of cumulative depression in a 24-h window indicated reversible delayed neurological deficit, only a 180-min cut-off indicated new infarction with >0.60 sensitivity and >0.80 specificity. Although spontaneous resolution of the neurological deficit is still possible, we recommend initiating rescue treatment at the 60-min rather than the 180-min cut-off if progression of injury to infarction is to be prevented.Focal damage after subarachnoid haemorrhage results from intracerebral haemorrhage and cerebral ischaemia. In a prospective, observational, multicentre, diagnostic phase III trial, DISCHARGE-1, Dreier et al. examine whether monitoring cortical spreading depolarizations can predict delayed infarction-and thus poor outcomes. LA - English DB - MTMT ER - TY - JOUR AU - Lemale, Coline L. AU - Lückl, János AU - Horst, Viktor AU - Reiffurth, Clemens AU - Major, Sebastian AU - Hecht, Nils AU - Woitzik, Johannes AU - Dreier, Jens P. TI - Migraine Aura, Transient Ischemic Attacks, Stroke, and Dying of the Brain Share the Same Key Pathophysiological Process in Neurons Driven by Gibbs–Donnan Forces, Namely Spreading Depolarization JF - FRONTIERS IN CELLULAR NEUROSCIENCE J2 - FRONT CELL NEUROSCI VL - 16 PY - 2022 PG - 29 SN - 1662-5102 DO - 10.3389/fncel.2022.837650 UR - https://m2.mtmt.hu/api/publication/32663200 ID - 32663200 LA - English DB - MTMT ER - TY - THES AU - Nyári, Csaba TI - Investigation of the risk factors of preterm birth and infant mortality in Hungary – epidemiological and cost-effectiveness analyses PB - Szegedi Tudományegyetem (SZTE) PY - 2015 SP - 44 DO - 10.14232/phd.2521 UR - https://m2.mtmt.hu/api/publication/2995653 ID - 2995653 LA - English DB - MTMT ER - TY - THES AU - Asztalos, Emese TI - Fotoszintetizáló baktériumok fluoreszcenciájának indukciója és relaxációja PB - Szegedi Tudományegyetem (SZTE) PY - 2015 SP - 123 DO - 10.14232/phd.2392 UR - https://m2.mtmt.hu/api/publication/2993027 ID - 2993027 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Kis, Mariann AU - Sipka, Gábor AU - Asztalos, Emese AU - Rázga, Zsolt AU - Maróti, Péter TI - Purple non-sulfur photosynthetic bacteria monitor environmental stresses JF - JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY J2 - J PHOTOCH PHOTOBIO B VL - 151 PY - 2015 SP - 110 EP - 117 PG - 8 SN - 1011-1344 DO - 10.1016/j.jphotobiol.2015.07.017 UR - https://m2.mtmt.hu/api/publication/2925398 ID - 2925398 LA - English DB - MTMT ER - TY - JOUR AU - Maróti, Ágnes AU - Wraight, CA AU - Maróti, Péter TI - Protonated rhodosemiquinone at the QB binding site of M265IT mutant reaction center of photosynthetic bacterium Rhodobacter sphaeroides JF - BIOCHEMISTRY J2 - BIOCHEMISTRY-US VL - 54 PY - 2015 IS - 12 SP - 2095 EP - 2103 PG - 9 SN - 0006-2960 DO - 10.1021/bi501553t UR - https://m2.mtmt.hu/api/publication/2865767 ID - 2865767 N1 - Megjegyzés-24740852 N1 Funding Details: CM1306, COST, Országos Tudományos Kutatási Alapprogramok N1 Funding Details: K116834, OTKA, Országos Tudományos Kutatási Alapprogramok AB - The 2nd electron transfer from the primary ubiquinone QA to the secondary ubiquinone QB in the reaction center (RC) from Rhodobacter sphaeroides involves protonated QB- intermediate state whose low pKa makes the direct observation impossible. Here, we replaced the native ubiquinone by low potential rhodoquinone at the QB binding site of the M265IT mutant RC. Because the in situ midpoint redox potential of QA of this mutant was lowered about the same extent ( approximately 100 mV) as that of QB upon exchange of ubiquinone by low potential rhodoquinone, the interquinone (QA-->QB) electron transfer became energetically favorable. After subsequent saturating flash excitations, a period of two damped oscillation of the protonated rhodosemiquinone was observed. The QBH* was identified by 1) the characteristic band at 420 nm of the absorption spectrum after the 2nd flash and 2) smaller damping of the oscillation at 420 nm (due to the neutral form) than at 460 nm (attributed to the anionic form). The appearance of the neutral semiquinone was restricted to the acidic pH range indicating a functional pKa of less than 5.5, slightly higher than that of the native ubisemiquinone (pKa < 4.5) at pH 7. The analysis of the pH- and temperature dependences of the rates of the 2nd electron transfer supports the concept of pH-dependent pKa of the semiquinone at the QB binding site. The local electrostatic potential is severely modified by the strongly interacting neighboring acidic cluster and the pKa of the semiquinone is in the middle of the pH range of the complex titration. The kinetic and thermodynamic data are discussed according to the proton-activated electron transfer mechanism combined with pH-dependent functional pKa of the semiquinone at the QB site of the RC. LA - English DB - MTMT ER - TY - JOUR AU - Maróti, Péter TI - A kék LED fizikai Nobel-díjat érdemelt JF - MAGYAR KÉMIKUSOK LAPJA J2 - MAGY KEM LAP VL - 70 PY - 2015 IS - 2 SP - 37 EP - 38 PG - 2 SN - 0025-0163 UR - https://m2.mtmt.hu/api/publication/2814951 ID - 2814951 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Gerencsér, László AU - Boros, Bogáta AU - Derrien, V AU - Hanson, DH AU - Wraight, CA AU - Sebban, P AU - Maróti, Péter TI - Stigmatellin probes the electrostatic potential in the QB site of photosynthetic reaction center JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 108 PY - 2015 IS - 2 SP - 379 EP - 394 PG - 16 SN - 0006-3495 DO - 10.1016/j.bpj.2014.11.3463 UR - https://m2.mtmt.hu/api/publication/2814945 ID - 2814945 LA - English DB - MTMT ER - TY - JOUR AU - Asztalos, Emese AU - Sipka, Gábor AU - Maróti, Péter TI - Fluorescence relaxation in intact cells of photosynthetic bacteria: donor and acceptor side limitations of reopening of the reaction center JF - PHOTOSYNTHESIS RESEARCH J2 - PHOTOSYNTH RES VL - 124 PY - 2015 IS - 1 SP - 31 EP - 44 PG - 14 SN - 0166-8595 DO - 10.1007/s11120-014-0070-0 UR - https://m2.mtmt.hu/api/publication/2814940 ID - 2814940 LA - English DB - MTMT ER - TY - JOUR AU - Maróti, Ágnes AU - Wraight, Colin A AU - Maróti, Péter TI - The rate of second electron transfer to QB− in bacterial reaction center of impaired proton delivery shows hydrogen-isotope effect JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS J2 - BBA-BIOENERGETICS VL - 1847 PY - 2015 IS - 2 SP - 223 EP - 230 PG - 8 SN - 0005-2728 DO - 10.1016/j.bbabio.2014.11.002 UR - https://m2.mtmt.hu/api/publication/2780613 ID - 2780613 AB - Abstract The 2nd electron transfer in reaction center of photosynthetic bacterium Rhodobacter sphaeroides is a two step process in which protonation of QB− precedes interquinone electron transfer. The thermal activation and pH dependence of the overall rate constants of different RC variants were measured and compared in solvents of water (H2O) and heavy water (D2O). The electron transfer variants where the electron transfer is rate limiting (wild type and M17DN, L210DN and H173EQ mutants) do not show solvent isotope effect and the significant decrease of the rate constant of the second electron transfer in these mutants is due to lowering the operational pKa of QB−/QBH: 4.5 (native), 3.9 (L210DN), 3.7 (M17DN) and 3.1 (H173EQ) at pH 7. On the other hand, the proton transfer variants where the proton transfer is rate limiting demonstrate solvent isotope effect of pH-independent moderate magnitude (2.11 ± 0.26 (WT + Ni2 +), 2.16 ± 0.35 (WT + Cd2 +) and 2.34 ± 0.44 (L210DN/M17DN)) or pH-dependent large magnitude (5.7 at pH 4 (L213DN)). Upon deuteration, the free energy and the enthalpy of activation increase in all proton transfer variants by about 1 kcal/mol and the entropy of activation becomes negligible in L210DN/M17DN mutant. The results are interpreted as manifestation of equilibrium and kinetic solvent isotope effects and the structural, energetic and kinetic possibility of alternate proton delivery pathways are discussed. LA - English DB - MTMT ER -