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Can a growing battery industry remain within planetary boundaries?
No full textThe rapid growth of the battery industry leads to a high demand for critical raw materials, an increasing amount of battery waste and environmental impacts along the value-chain. Several life cycle assessments have compared the relative environmental impacts of different battery technologies, production processes, or locations. However, an assessment of the environmental impacts of batteries on a planetary scale is missing. Therefore, we provide a connection between the environmental impacts of the potentially circular battery value chain and the planetary boundaries framework. Transgression of planetary boundaries will lead the Earth down an unstable path, which should be avoided. While the use of batteries in the automotive industry has significant positive impact on the environmental footprint, the battery production will clearly transgress its assigned share of the safe operating space in three planetary boundaries in 2030, 2035 and 2040 on its current trajectory. Consumption of critical raw materials accounts for most of the planetary footprint, encouraging the development of sodium-ion batteries and circular economy strategies. Alongside high recycling rates, the consequent implementation of process innovations, such as dry coating and direct lithium extraction, and the use of renewable energy will reduce the transgression of planetary boundaries. Still, further efforts are required to bring the battery industry in line with its safe operating space for phosphorous cycle and climate change. To avoid the prospect of strict policy interventions, our work encourages the fast-growing battery industry to assess innovations and demand projections through a planetary boundary lens
Characterization of pre-existing anti-PEG and anti-AGAL antibodies towards PRX-102 in patients with Fabry disease
No full textPolyethylene glycol (PEG)ylated drugs are used for medical treatment, since PEGylation either decreases drug clearance or/and shields the protein from undesirable immunogenicity. PEGylation was implemented in a new enzyme replacement therapy for Fabry disease (FD), pegunigalsidase-alfa (PRX-102). However, exposure to PEG via life-style products and vaccination can result in the formation of anti-PEG antibodies. We demonstrate the 'de novo' formation of functional anti-PEG antibodies in a healthy male after the second mRNA-based vaccination against SARS-CoV-2. Consequently, we analyzed the frequency and inhibitory function of anti-PEG and anti-α-Galactosidase A (AGAL) antibodies in 102 FD patients (46.9% males). We identified 29 out of 87 (33.3%) patients with low anti-PEG titers. Sera from patients without anti-AGAL antibodies [n=70] showed a higher rescued AGAL activity of agalsidase-beta and PRX-102 [both p<0.0001] compared to those with anti-AGAL antibodies [n=15]. Sera from anti-AGAL antibody-negative and -positive patients had less inhibitory effects on PRX-102 (rescued activity: 89 ± 6% versus 85 ± 7% and 49 ± 26% versus 25 ± 32%; both p<0.0001). Enzyme stability assays demonstrated that AUCs in anti-AGAL-negative sera (n=20) were 7.6-fold higher for PRX-102, while AUCs of both enzymes in anti-AGAL-positive sera (n=6) were decreased. However, AUC for PRX-102 was 33% of non-anti-AGAL-positive sera treated PRX-102 and 5-fold higher compared to agalsidase-beta. Anti-PEG antibodies had no significant effects on serum half-life of PRX-102, probably due to low titers. Conceivably, therapy efficacy may be superior under next-generation PRX-102 therapy compared to current enzyme replacement therapies in terms of reduced inhibitory effects of anti-AGAL and minor inhibitory effects of anti-PEG antibodies
Characterization of the interaction between Liver Kinase B1 and Lethal (2) giant larvae in 'Drosophila melanogaster'
No full textDer Verlust von Zellpolarität und die Degeneration der Gewebearchitektur spielen eine wesentliche Rolle für die Entstehung, Wachstum und Ausbreitung von Tumoren.
Insbesondere maligne Karzinomzellen, welche aus Epithelgewebe hervorgehen, zeigen einen Verlust der apikal-basalen Polarität und ein Ablösen vom zellulären Netzwerk.
Die epithelial-mesenchymale Transition, welche die Migration von Epithelzellen ermöglicht, führt zu aggressiveren Tumorphänomenen mit entdifferenzierten Zellen bis hin zu anaplastischen Zelltypen.
Die Masterkinase LKB1 und Lgl, ein Mitglied des Scribble-Komplexes, die beide als Tumorsuppressorproteine bekannt sind, sind essenziell für die Aufrechterhaltung der Zellpolarität.
Vorangegangene Untersuchungen lassen vermuten, dass Lgl ein nachgeschaltetes Phosphorylierungsziel von LKB1 ist und dessen Einflussnahme auf die Zellpolarität unterstützt. Nachfolgend wird die Interaktion beider Proteine im Modellorganismus Drosophila melanogaster weitergehend untersucht
Contactin-associated protein 2 autoantibodies can be associated with multifocal motor-like neuropathy: a case report
No full textAutoantibodies against contactin-associated protein 2 (CASPR2) are usually associated with autoimmune encephalitis and neuromyotonia. Their association with inflammatory neuropathies has been described in case reports albeit all with distal symmetric manifestation. Here, we report a patient who developed distal arm paresis, dominantly of the right arm, over the course of 1 year. Electroneurography showed a conduction block of motor nerve conduction, nerve ultrasonography a swelling of the right median and ulnar nerve and flow cytometry an increase in natural killer (NK cells) in the blood and natural killer T (NKT) cells in the cerebrospinal fluid (CSF), therefore indicating a multifocal motor neuropathy-like (MMN-like) phenotype. CASPR2 autoantibodies were detected in serum and CSF. Through immunotherapy with intravenous immunoglobulins the patient showed clinical and neurographic improvement. We therefore describe the first association of CASPR2 autoantibodies with a MMN-like clinical manifestation, extending the spectrum of CASPR2-associated diseases
Different propensities for gate opening in gyrases and topoisomerase IV
No full textThe bacterial type IIA topoisomerases gyrase and topoisomerase IV (Topo IV) catalyze DNA supercoiling and decatenation (gyrase), or DNA relaxation and decatenation (Topo IV) in ATP-dependent reactions. Most bacteria contain both gyrase and Topo IV, which jointly remove torsional stress during replication: gyrase removes positive supercoils ahead of the replication fork, while Topo IV decatenates pre-catenanes behind the fork and the catenated daughter chromosomes. Some bacteria, including 'Mycobacterium tuberculosis', contain only a gyrase, which then needs to perform both reactions. The molecular determinants for the predominant activity of type IIA topoisomerases are unclear. We hypothesize that the prevalent activity is connected to the stabilities of the DNA- and C-gates. In a comparative single-molecule FRET study of 'Bacillus subtilis' and 'M. tuberculosis' gyrase and 'B. subtilis' Topo IV, we show that the DNA-gates are less stable than the C-gates in all three enzymes. The stabilities of the DNA-gates of gyrase and Topo IV are similar. Strikingly, the C-gates in both gyrases are highly stable, but the C-gate in Topo IV is markedly less stable. Our results suggest that the stability of the C-gate of type IIA topoisomerases is linked to their activities
Drosophila hedgehog signaling range and robustness depend on direct and sustained heparan sulfate interactions
No full textMorphogens determine cellular differentiation in many developing tissues in a concentration dependent manner. As a central model for gradient formation during animal development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in the 'Drosophila' wing disc. Although heparan sulfate (HS) expression in the disc is essential for this process, it is not known whether HS regulates Hh signaling and spread in a direct or in an indirect manner. To answer this question, we systematically screened two composite Hh binding areas for HS in vitro and expressed mutated proteins in the 'Drosophila' wing disc. We found that selectively impaired HS binding of the second site reduced Hh signaling close to the source and caused striking wing mispatterning phenotypes more distant from the source. These observations suggest that HS constrains Hh to the wing disc epithelium in a direct manner, and that interfering with this constriction converts Hh into freely diffusing forms with altered signaling ranges and impaired gradient robustness
Early ERPs dissociate subjectively nonconscious low- and high-level face processing
No full textThere is an ongoing debate about the extent to which faces are processed if they are not consciously perceived. In the present study, we used event-related potentials (ERPs) to investigate neural responses to faces and two types of control stimuli (monochrome color-matched ovals and Fourier phase-scrambled faces), which allowed us to dissociate low-level and high-level face processing. Based on a pre-registered sequential Bayesian sampling protocol, we recorded the electroencephalogram (EEG) from 40 participants and compared the average amplitude of early components of the ERP (P1, N170) between faces, scrambles, and blanks presented for 17 ms, while the mask followed directly or 200 ms after the target stimulus. Participants were asked to rate their subjective perception after each trial on a perceptual awareness scale, and only trials with the lowest rating in the masked condition were considered as subjectively nonconscious. Matching the pre-registered hypotheses, P1 amplitudes were higher for faces and scrambles compared to blanks but did not differ between faces and scrambles. This pattern was found for conscious and nonconscious faces, however, with smaller yet reliable differences in the latter case. In contrast, the N170 reliably differentiated between faces and both types of control stimuli (scrambles and blanks), again for conscious and, with attenuated differences, also for nonconscious faces. Findings support the hypothesis of two early stages of face processing, which are at least partially independent of consciousness awareness of stimuli. The P1 stage is associated with low-level processing, while the N170 reflects processing of face-related configural information
Educational Governance: Beteiligungschance für Zivilgesellschaft im deutschen Schulsystem
No full textDie Dissertation beleuchtet das Handlungsfeld Bildung innerhalb der organisierten Zivilgesellschaft in Deutschland. Ausgehend von einem empirischen Forschungsdesiderat analysiert sie zunächst den Wandel der bildungspolitischen Rahmenbedingungen für zivilgesellschaftliche Organisationen seit den 1990er Jahren. Anschließend wird untersucht, wie sich das Handlungsfeld Bildung vor dem Hintergrund dieser Veränderungen strukturell und inhaltlich transformiert. Im Zentrum stehen zivilgesellschaftliche Akteure wie Vereine, Stiftungen und gGmbHs, die zunehmend als Bildungspartner in das öffentliche Schulsystem eingebunden werden. Die Arbeit verknüpft theoretische Perspektiven aus der Governance-Forschung mit empirischen Daten, insbesondere aus dem ZiviZ-Survey. Auf Basis von sechs Einzelbeiträgen zeigt die Dissertation, dass Bildung ein dynamisch wachsendes, bislang jedoch wenig erforschtes Handlungsfeld der Zivilgesellschaft ist – geprägt von staatlicher Steuerung, institutionellen Öffnungsprozessen und neuen Kooperationsformen. Die Arbeit leistet damit einen Beitrag zur Integration von Bildungs- und Zivilgesellschaftsforschung und liefert Impulse für Theorie, Empirie und Praxis.This dissertation explores the field of education within the organized civil society in Germany. Starting from an empirical research gap, it first analyzes how education policy frameworks for civil society organizations have evolved since the 1990s. It then examines how these changing conditions are transforming the field of education itself. The focus lies on civil society actors such as associations, foundations, and nonprofit limited liability companies (gGmbHs), which are increasingly integrated as educational partners within the public school system. The study combines theoretical approaches from governance research with empirical data, notably from the ZiviZ Survey and other studies. Across six individual contributions, the dissertation demonstrates that education is a growing yet underexplored field of civil society activity—characterized by state steering, institutional openings, and new forms of cooperation. It contributes to bridging the gap between education and civil society research and provides insights for theory, empirical inquiry, and practice
Evaluation of effectiveness and safety of the large-format pRESET 6-50 thrombectomy stent-retriever in the endovascular treatment of ischemic stroke: real-world experiences from two tertiary comprehensive stroke centers
No full textObjective: Mechanical thrombectomy (MT) has become the standard treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO). First-pass (FP) reperfusion of the occluded vessel and fewer passes with stent retrievers show improvement in functional outcomes in stroke patients, while higher numbers of passes are associated with higher complication rates and worse outcomes. Studies indicate that a larger size of the stent-retriever is associated with a higher rate of first-pass reperfusion and improved clinical outcomes. In this retrospective study, we investigated the clinical performance of a recently developed and one of the largest stent-retrievers available in the treatment of LVO (pRESET 6-50, phenox GmbH, Bochum). Materials and methods: All consecutive patients with ischemic stroke due to proximal large vessel occlusion treated with MT using the pRESET 6-50 stent-retriever in two tertiary stroke centers between 09/2021 and 07/2022 were included in this study. The reperfusion rate after MT was quantified by the modified thrombolysis in cerebral infarction (mTICI) score, and functional neurological outcome was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score and the major early neurological recovery (mENR) rate after 24 h. Successful FP reperfusion was defined as mTICI ≥ 2b. Successful and complete reperfusion were defined as mTICI ≥ 2b and mTICI ≥ 2c, respectively. Results: In total, 98 patients (52 men and 46 women) with a median age of 75 (range 25–95 years) were included. A total of 70 (72%) patients presented with an occlusion of the middle cerebral artery (MCA) in the M1 segment, 6 (6%) patients with an occlusion of the M2 segment, 17 (17%) patients with an occlusion of the internal carotid artery (ICA), and 5 (5%) patients with an occlusion of the obstructed basilar artery (BA). Successful FP reperfusion was achieved in 58 patients (62%). Successful and complete reperfusion were achieved in 95 (97%) and 82 (83%) patients, respectively. The median National Institutes of Health Stroke Scale (NIHSS) in all treated patients improved from 17 to 7.5. Major early neurological recovery (mENR) was observed in 34 patients (35.1%). Conclusion: MT with the pRESET 6-50 stent-retriever achieves high successful first-pass and final reperfusion rates in patients with AIS and LVO. The results of this study support the thesis to use large-format stent-retriever in proximal vessel occlusion MT whenever feasible in order to improve high FP and final reperfusion rate, which are known predictors of good clinical outcome