26 results on '"Schäfer, Lisa"'
Search Results
2. Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.
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Bergner, Caroline G, Breur, Marjolein, Soto-Bernardini, M Clara, Schäfer, Lisa, Lier, Julia, Duc, Diana Le, Bundalian, Linnaeus, Schubert, Susanna, Brenner, David, Kreuz, Friedmar R, Schulte, Björn, Waisfisz, Quinten, Bugiani, Marianna, Köhler, Wolfgang, Sticht, Heinrich, Jamra, Rami Abou, and Knaap, Marjo S van der
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LEUKOENCEPHALOPATHIES ,WHITE matter (Nerve tissue) ,CORPUS callosum ,CYSTATIN C ,GLOBUS pallidus ,LEUKODYSTROPHY ,CEREBRAL amyloid angiopathy - Abstract
Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. This perception has been altered in recent years, as a growing number of leukodystrophies have been described as having an onset in adulthood. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16 patients from eight families carrying one of four different stop-gain or frameshift dominant variants in the CST3 gene. Clinical and radiological features differ markedly from the previously described Icelandic cerebral amyloid angiopathy found in patients carrying p.Leu68Asn substitution in CST3. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid to older adult ages. In addition, in some cases acute onset clinical deterioration led to a prolonged episode with reduced consciousness and even early death. Radiologically, pathognomonic changes are found at typical predilection sites involving the deep cerebral white matter sparing a periventricular and directly subcortical rim, the middle blade of corpus callosum, posterior limb of the internal capsule, middle cerebellar peduncles, cerebral peduncles and specifically the globus pallidus. Histopathologic characterization in two autopsy cases did not reveal angiopathy, but instead micro- to macrocystic degeneration of the white matter. Astrocytes were activated at early stages and later displayed severe degeneration and loss. In addition, despite the loss of myelin, elevated numbers of partly apoptotic oligodendrocytes were observed. A structural comparison of the variants in CST3 suggests that specific truncations of cystatin C result in an abnormal function, possibly by rendering the protein more prone to aggregation. Future studies are required to confirm the assumed effect on the protein and to determine pathophysiologic downstream events at the cellular level. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Topic drop in German: Empirical support for an information-theoretic account to a long-known omission phenomenon
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Schäfer Lisa
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topic drop ,ellipsis ,information theory ,uniform information density hypothesis ,predictability ,recoverability ,corpus study ,acceptability judgments ,Language. Linguistic theory. Comparative grammar ,P101-410 - Abstract
German allows for topic drop (Fries 1988), the omission of a preverbal constituent from a V2 sentence. I address the underexplored question of why speakers use topic drop with a corpus study and two acceptability rating studies. I propose an information-theoretic explanation based on the Uniform Information Density hypothesis (Levy and Jaeger 2007) that accounts for the full picture of data. The information-theoretic approach predicts that topic drop is more felicitous when the omitted constituent is predictable in context and easy to recover. This leads to a more optimal use of the hearer’s processing capacities. The corpus study on the FraC corpus (Horch and Reich 2017) shows that grammatical person, verb probability and verbal inflection impact the frequency of topic drop. The two rating experiments indicate that these differences in frequency are also reflected in acceptability and additionally evidence an impact of topicality on topic drop. Taken together my studies constitute the first systematic empirical investigation of previously only sparsely researched observations from the literature. My information-theoretic account provides a unifying explanation of these isolated observations and is also able to account for the effect of verb probability that I find in my corpus study.
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- 2021
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4. Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma
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Gagelmann, Nico, primary, Dima, Danai, additional, Merz, Maximilian, additional, Hashmi, Hamza, additional, Ahmed, Nausheen, additional, Tovar, Natalia, additional, Oliver-Caldés, Aina, additional, Stölzel, Friedrich, additional, Rathje, Kristin, additional, Fischer, Luise, additional, Born, Patrick, additional, Schäfer, Lisa, additional, Albici, Anca-Maria, additional, Schub, Natalie, additional, Kfir-Erenfeld, Shlomit, additional, Assayag, Miri, additional, Asherie, Nathalie, additional, Wulf, Gerald Georg, additional, Kharboutli, Soraya, additional, Müller, Fabian, additional, Shune, Leyla, additional, Davis, James A., additional, Anwer, Faiz, additional, Vucinic, Vladan, additional, Platzbecker, Uwe, additional, Ayuk, Francis, additional, Kröger, Nicolaus, additional, Khouri, Jack, additional, Gurnari, Carmelo, additional, McGuirk, Joseph, additional, Stepensky, Polina, additional, Abdallah, Al-Ola, additional, and Fernández de Larrea, Carlos, additional
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- 2024
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5. Survival benefit with checkpoint inhibitors versus chemotherapy is modified by brain metastases in patients with recurrent small cell lung cancer
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Althoff, Friederike C., primary, Schäfer, Lisa V., additional, Acker, Fabian, additional, Aguinarte, Lukas, additional, Heinzen, Sophie, additional, Rost, Maximilian, additional, Atmaca, Akin, additional, Rosery, Vivian, additional, Alt, Jürgen, additional, Waller, Cornelius F., additional, Reinmuth, Niels, additional, Rohde, Gernot, additional, Saalfeld, Felix C., additional, Becker von Rose, Aaron, additional, Möller, Miriam, additional, Frost, Nikolaj, additional, Sebastian, Martin, additional, and Stratmann, Jan A., additional
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- 2023
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6. Editorial: White matter dementia: neuropathological and neuropsychological underpinnings and state of the art diagnosis methods and treatments
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Filley, Christopher M., primary, Penner, Iris-Katharina, additional, Schäfer, Lisa, additional, and Köhler, Wolfgang, additional
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- 2023
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7. Case report: Treatment of advanced CSF1-receptor associated leukoencephalopathy with hematopoietic stem cell transplant
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Bergner, Caroline G., primary, Schäfer, Lisa, additional, Vucinic, Vladan, additional, Schetschorke, Birthe, additional, Lier, Julia, additional, Scherlach, Cordula, additional, Rullmann, Michael, additional, Sabri, Osama, additional, Classen, Joseph, additional, Platzbecker, Uwe, additional, Kühl, Jörn-Sven, additional, Barthel, Henryk, additional, Köhler, Wolfgang, additional, and Franke, Georg-Nikolaus, additional
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- 2023
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8. Self‐reported quality of life in symptomatic and asymptomatic women with X‐linked adrenoleukodystrophy
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Schäfer, Lisa, primary, Roicke, Hannes, additional, Bergner, Christa‐Caroline, additional, and Köhler, Wolfgang, additional
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- 2023
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9. Food-Induced Brain Activity in Children with Overweight or Obesity versus Normal Weight: An Electroencephalographic Pilot Study
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Kösling, Christine, primary, Schäfer, Lisa, additional, Hübner, Claudia, additional, Sebert, Caroline, additional, Hilbert, Anja, additional, and Schmidt, Ricarda, additional
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- 2022
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10. Verb predictability effects on the usage of gapping (production study)
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Bozhidara Hristova, Lemke, Robin, Drenhaus, Heiner, Reich, Ingo, and Schäfer, Lisa
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Psycholinguistics and Neurolinguistics ,German Language and Literature ,FOS: Languages and literature ,Linguistics ,Arts and Humanities ,German Linguistics ,Social and Behavioral Sciences - Abstract
The study has two goals. First, it tests whether the usage of gapping is subject to the information-theoretic processing constraint of Uniform Information Density (UID, Levy and Jaeger, 2007). UID predicts that gapping is more strongly preferred and easier to process the more predictable the potentially omitted verb is. Second, it serves the purpose of norming stimuli for follow-up acceptability rating and self-paced reading experiments. We measure and aim at manipulating the surprisal (-log 2 p(verb|context)) of the verb in the second conjunct of clausal coordinations like (1) given its subject and the first conjunct of the coordination. (1) The boxer beat up an opponent and the (hooligan|hippie)______. (Note that in German, unlike in English, the example is not ambiguous due to the case marking at the subject) We manipulate the surprisal of the target verb through the typicality of the second conjunct's subject as a subject of this verb (it is more typical for a hooligan to beat up people than for a hippie). In our study, we present the participants with German clausal coordinations equivalent to (1) that are cut off after the subject of the second conjunct. In a one-factor, two-level design, we will manipulate the typicality of the second conjunct's subject (prototypical/non-prototypical) in relation to the verb of the first conjunct. We expect that participants produce the same verb as the one in the first conjunct more often when the subject of the second conjunct is prototypical with regard to the verb. We also expect that the ratio of gapping produced by participants increases as a function of the verb's predictability. The typicality manipulation is based on our intuitions and the experiment allows us to investigate whether these intuitions are empirically supported.
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- 2023
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11. Verb predictability effects on the usage of gapping (rating study)
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Bozhidara Hristova, Lemke, Robin, Drenhaus, Heiner, Reich, Ingo, and Schäfer, Lisa
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German Language and Literature ,FOS: Languages and literature ,Linguistics ,Arts and Humanities ,Applied Linguistics ,German Linguistics ,Social and Behavioral Sciences - Abstract
The goal of the experiment is to explore whether the information-theoretic concept of Uniform Information Density (UID, Levy and Jaeger, 2007) explains the acceptability of gapping. According to the Uniform Information Density (UID) principle, speakers tend to spread information as evenly as possible across the linguistic signal. As a result, speakers try to avoid regions of low information by omitting predictable material from the utterance, i.e. by using an ellipsis. With respect to gapping, this predicts that listeners particularly prefer a gapped coordination when the verb of the second conjunct is predictable. We will test this prediction with an acceptability rating study. In a 2x2 design, we will cross the surprisal of the verb (high/low) with the form of the sentence (nonelliptical/gapping). We will manipulate the surprisal of the verb given the subject noun phrase though world knowledge, more specifically - through the typicallity of the subject. We expect that gapping is rated as relatively more acceptable (compared to the nonelliptical form) when the verb of the second conjunct is predictable. A production study ("Verb predictability effects on the usage of gapping (production study)", preregistered separately on OSF) will be used to measure the surprisal of the verb given the preceding context, which is used as a predictor in our analyses.
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- 2023
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12. Coordination ellipsis, modality and memory (acceptability rating) - Exp. 2
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Lemke, Robin, Reich, Ingo, Schäfer, Lisa, and Drenhaus, Heiner
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Psycholinguistics and Neurolinguistics ,German Language and Literature ,FOS: Languages and literature ,Linguistics ,Arts and Humanities ,German Linguistics ,Social and Behavioral Sciences - Abstract
This is a follow-up acceptability rating study to "Coordination ellipsis, modality and memory (acceptability rating) - Exp. 1" (also preregistered). Experiment 1 investigates the hypothesis that the relatively stronger preference for coordination ellipsis (and particularly right node raising) in written corpus data as compared to spoken corpora (Harbusch 2011) is explained by the possibility of backtracking in written language. If this is expectation is confirmed, we will investigate in experiment 2 whether processing coordination ellipsis is indeed inhibited by memory limitations, which are counterbalanced by backtracking in the written modality. To this end, we will explicitly manipulate the memory load of our participants in a replication of the oral conditions of experiment 1: Half of our participants will be asked to perform mathematical calculations between the trials and to memorize the result in order to later (after 1 to 3 trials) enter it into a text field. We expect that participants whose memory is partly used for this additional task will prefer more explicit, i.e. non-elliptical, structures more strongly than participants who do not need to memorize the results. We expect that this effect is particularly strong for right node raising, since this construction requires comprehenders to keep the incomplete first conjunct in their working memory until the expression filling the gap is encountered.
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- 2023
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13. Interpretation of German masculine personal nouns: Gender bias vs prosody
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Rauth, Philipp, Schäfer, Lisa, and Lemke, Robin
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Psycholinguistics and Neurolinguistics ,German Language and Literature ,FOS: Languages and literature ,Linguistics ,Arts and Humanities ,German Linguistics ,Social and Behavioral Sciences - Abstract
The experiment investigates the interpretation of German plural masculine nouns referring to a group of people (e.g. the actors, the teachers) in an experimental paradigm based on Gygax et al. (2008) and Körner et al. (2022). Based on binary sentence continuation judgment tasks these studies conclude that such masculine nouns are more often interpreted as referring only to male referents than generically, that is, possibly including females. Our experiment addresses a possible design flaw of the studies by Gygax et al. (2008) and Körner et al. (2022) which consists in a purely written presentation of the stimuli which does not control for prosody. We present similar stimuli auditorily in two conditions, one of which (unmarked intonation pattern) suggests that the group in the target utterance is only male or female, whereas we expect that the other one (contrastive topic intonation) indicates a gender-mixed interpretation of the masculine nouns. This will reveal to what extent previous findings depend on the unmarked intonation pattern, which is assumed to be the default prosodic structure in silent reading (Féry 2005). The main experiment will be followed by a questionnaire to determine the participants' attitude toward gender-neutral language and their explicit interpretation of the generic masculine forms.
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- 2022
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14. Resistance Drift Convergence and Inversion in Amorphous Phase Change Materials
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Pries, Julian, primary, Stenz, Christian, additional, Schäfer, Lisa, additional, Gutsche, Alexander, additional, Wei, Shuai, additional, Lucas, Pierre, additional, and Wuttig, Matthias, additional
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- 2022
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15. Tabakregulierung zwischen Kooperation und Konfrontation - Framing- und prozessanalytische Perspektiven zur Identifikation von Erfolgsfaktoren für Interessenvertretung in der Europäischen Union
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Schäfer, Lisa and Bieling, Hans-Jürgen (Prof. Dr.)
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framing ,Interest representation ,Lobbying ,Prozessanalyse ,Interessenforschung ,process tracing ,EU ,Tabakindustrie ,tobacco ,Interessenvertretung - Abstract
Die Partizipation von Interessengruppen in Gesetzgebungsprozessen der Europäischen Union (EU) ist von gegenseitiger Abhängigkeit im Sinne eines politischen Tauschs geprägt: Die gesetz-gebenden Institutionen benötigen Fachinformationen zur politischen Entscheidungsfindung. Inte-ressengruppen liefern Informationen und erhoffen sich dadurch Einfluss auf das Politikergebnis. Angesichts der Flut an konkurrierenden Akteuren, die auf diesen diskursiven Tausch einwirken, beschäftigt sich diese Arbeit mit der Frage, welche Faktoren politische Einflussnahme begünsti-gen. Dabei liegt die Annahme zugrunde, dass Interessengruppen versuchen, vor allem diskursi-ve Macht zu mobilisieren, um gesetzgebende Akteure zu überzeugen. Ihr Erfolg variiert je nach-dem, ob sie in der Lage sind, Koalitionen zu schmieden, politische Ansprechpartner zu finden und Informationen bereitzustellen. Um ihren Botschaften dabei mehr politisches Profil zu geben, nutzen sie Framing. Am Beispiel der Revision der EU-Tabakrichtlinie von 2012-2014 befasst sich diese Arbeit mit dem analytischen Potenzial der Erfolgsfaktoren politischer Einflussnahme in einem dynamischen Setting. Dazu wurde der Gesetzgebungsprozess in vier Analysephasen unterteilt und metho-disch mithilfe einer Kombination aus Prozessanalyse und dem Abgleich von Framing zwischen Interessengruppen und Institutionen, kurz Framing-Analyse, aufbereitet. Die Tabakrichtlinie polarisierte den politischen Diskurs und gilt heute als exemplarischer Kasus für intensives Lobbying, bei dem die Interessen von Tabakindustrie und Verbraucherschutz-Gruppen aufeinanderprallten. Die ausgezeichnete Quellenlage bereitete die Basis für die Anwen-dung der Methodenkombination, die zu teils überraschenden Erkenntnissen kommt. Erstens erwiesen sich formelle Koalitionen für erfolgreiche Interessenvertretung im vorliegenden Fall als weniger bedeutsam als angenommen. Wichtiger sind einheitliche Botschaften, die von einer möglichst heterogenen Gruppe aus Akteuren reproduziert werden. Zweitens sind möglichst exklusive Kontakte zu politischen Schlüsselfiguren von großem Vorteil. Allerdings versuchen Interessenvertreter auch über die Ansprache fachfremder politischer Akteure innerhalb der Insti-tutionen Einfluss auszuüben und innerinstitutionelle Opposition zu generieren. Diese Strategie führte im untersuchten Fall zum Erfolg – ausgerechnet das Europäische Parlament schwächte den Gesetzentwurf der Kommission an entscheidenden Stellen ab. Drittens begünstigt die Fä-higkeit, relevante Informationen bereitzustellen, die Chancen auf Einflussnahme. Interessen-gruppen nutzen Framing dabei gezielt zur Zuspitzung und Legitimierung ihrer Forderungen sowie zur Abgrenzung von konkurrierenden Interessen. Die Kombination aus Prozess- und Framing-Analyse erlaubt im Gegensatz zu vielen Large-N Studien eine Fokussierung auf mehrere Variablen, die als Erklärungsfaktoren politischer Ein-flussnahme dienen, und trägt gleichzeitig dazu bei, eine Triangulation der Befunde zu gewährleis-ten. Angesichts der zunehmenden Partizipation organisierter Interessen an EU-Gesetzgebungsprozessen, leistet diese Arbeit einen relevanten Beitrag zu einem dynamischen Verständnis von Interessenvertretung und bietet eine neue methodische Perspektive zur weite-ren Erforschung von Interessenvertretung in der EU.
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- 2022
16. Teachers involved in school improvement: Analyzing mediating mechanisms of teachers’ boundary-crossing activities between leadership perception and teacher involvement
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Rechsteiner, Beat, primary, Compagnoni, Miriam, additional, Wullschleger, Andrea, additional, Schäfer, Lisa Maria, additional, Rickenbacher, Ariane, additional, and Maag Merki, Katharina, additional
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- 2022
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17. Teachers involved in school improvement: Analyzing mediating mechanisms of teachers’ boundary-crossing activities between leadership perception and teacher involvement
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Rechsteiner, Beat; https://orcid.org/0000-0003-2555-431X, Compagnoni, Miriam; https://orcid.org/0000-0002-7850-129X, Wullschleger, Andrea; https://orcid.org/0000-0003-4390-3835, Schäfer, Lisa Maria, Rickenbacher, Ariane, Maag Merki, Katharina; https://orcid.org/0000-0002-0215-1684, Rechsteiner, Beat; https://orcid.org/0000-0003-2555-431X, Compagnoni, Miriam; https://orcid.org/0000-0002-7850-129X, Wullschleger, Andrea; https://orcid.org/0000-0003-4390-3835, Schäfer, Lisa Maria, Rickenbacher, Ariane, and Maag Merki, Katharina; https://orcid.org/0000-0002-0215-1684
- Abstract
Teachers are drivers for change in school improvement. However, not all teachers participate in further developing schools' educational practice. This study aimed to understand conditional factors in teachers' involvement. To this end, we analyzed teachers' leadership perception and boundary-crossing activities aimed at increasing professional capital. Structural equation modeling analyses based on a sample of N = 1232 teachers at N = 59 schools indicated partial mediations of cognitive and social boundary-crossing activities on the relationship between leadership perception and involvement. This study contributes to the literature by illuminating the potential of teachers’ activities to enhance professional capital for school improvement.
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- 2022
18. Coordination ellipsis, modality and memory (acceptability rating) - Exp. 1
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Lemke, Robin, Reich, Ingo, Schäfer, Lisa, and Drenhaus, Heiner
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Psycholinguistics and Neurolinguistics ,German Language and Literature ,FOS: Languages and literature ,Linguistics ,German Linguistics ,Arts and Humanities ,Social and Behavioral Sciences - Abstract
We will conduct an acceptability rating study to test whether ellipsis, in particular right node raising, but also gapping, is rated as more acceptable (as compared to the nonelliptical utterance, in what follows "full form", as baseline) in written than in oral modality due to memory considerations. The idea is that while in the written modality the addressee can reread parts of the utterance, i.e., perform backtracking, this is not possible in the oral modality where the addressee hears an utterance exactly once. Therefore, more explicit full forms might be more strongly preferred over ellipsis in oral modality. This should be especially true for RNR where hearers have to keep the incomplete first conjunct in memory until encountering the missing material and completing its processing. We will compare not only oral and written modality, but also include a written, but timed word-by-word presentation (timed written). This will show whether the expected difference between written and oral modality is due to the availability of backtracking (as we expect) or to other differences between the modalities.
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- 2022
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19. Was zeichnet eine hohe Schulentwicklungskapazität aus?
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Maag Merki, Katharina, Schäfer, Lisa, Rechsteiner, Beat, Wullschleger, Andrea, Compagnoni, Miriam, Rickenbacher, Ariane, and University of Zurich
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10091 Institute of Education ,370 Education - Published
- 2022
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20. Teachers involved in school improvement: Analyzing mediating mechanisms of teachers’ boundary-crossing activities between leadership perception and teacher involvement
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Rechsteiner, Beat, Compagnoni, Miriam, Wullschleger, Andrea, Schäfer, Lisa Maria, Rickenbacher, Ariane, Maag Merki, Katharina, University of Zurich, and Rechsteiner, Beat
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leadership role ,Teacher involvement ,10091 Institute of Education ,school improvement ,370 Education ,teacher participation ,boundary crossing ,3304 Education ,professional development ,Education - Published
- 2022
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21. Reducing indoor particle exposure using mobile air purifiers—Experimental and numerical analysis
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Tobisch, Adrian, primary, Springsklee, Lukas, additional, Schäfer, Lisa-Franziska, additional, Sussmann, Nico, additional, Lehmann, Martin J., additional, Weis, Frederik, additional, Zöllner, Raoul, additional, and Niessner, Jennifer, additional
- Published
- 2021
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22. Thermally Controlled Charge‐Carrier Transitions in Disordered PbSbTe Chalcogenides
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Evang, Valentin, primary, Reindl, Johannes, additional, Schäfer, Lisa, additional, Rochotzki, Alexander, additional, Pletzer‐Zelgert, Pauline, additional, Wuttig, Matthias, additional, and Mazzarello, Riccardo, additional
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- 2021
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23. Thermally Controlled Charge‐Carrier Transitions in Disordered PbSbTe Chalcogenides.
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Evang, Valentin, Reindl, Johannes, Schäfer, Lisa, Rochotzki, Alexander, Pletzer‐Zelgert, Pauline, Wuttig, Matthias, and Mazzarello, Riccardo
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- 2022
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24. Was zeichnet eine hohe Schulentwicklungskapazität aus?
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MERKI, KATHARINA MAAG, SCHÄFER, LISA, RECHSTEINER, BEAT, WULLSCHLEGER, ANDREA, COMPAGNONI, MIRIAM, and RICKENBACHER, ARIANE
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SCHOOL administration ,EDUCATIONAL leadership ,TEACHERS ,DIGITAL technology ,STRATEGIC planning ,STUDENTS - Abstract
The article discusses what characterizes a high school development capacity. Topics include scientific findings on school development that promote learning show that it is not a single factor that is important, but that a combination of different factors is necessary so that schools can change sustainably; the lack of digital skills of the teachers; and efforts of teachers and school leaders as well as in school teams with regard to improving teaching and the support strategies of students.
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- 2022
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25. Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.
- Author
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Bergner CG, Breur M, Soto-Bernardini MC, Schäfer L, Lier J, Le Duc D, Bundalian L, Schubert S, Brenner D, Kreuz FR, Schulte B, Waisfisz Q, Bugiani M, Köhler W, Sticht H, Abou Jamra R, and van der Knaap MS
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Aged, Leukoencephalopathies genetics, Leukoencephalopathies pathology, Magnetic Resonance Imaging, Age of Onset, White Matter pathology, White Matter diagnostic imaging, Brain pathology, Brain diagnostic imaging, Pedigree, Cerebral Amyloid Angiopathy genetics, Cerebral Amyloid Angiopathy pathology, Cystatin C genetics
- Abstract
Leukodystrophies are rare genetic white matter disorders that have been regarded as mainly occurring in childhood. This perception has been altered in recent years, as a growing number of leukodystrophies have been described as having an onset in adulthood. Still, many adult patients presenting with white matter changes remain without a specific molecular diagnosis. We describe a novel adult onset leukodystrophy in 16 patients from eight families carrying one of four different stop-gain or frameshift dominant variants in the CST3 gene. Clinical and radiological features differ markedly from the previously described Icelandic cerebral amyloid angiopathy found in patients carrying p.Leu68Asn substitution in CST3. The clinical phenotype consists of recurrent episodes of hemiplegic migraine associated with transient unilateral focal deficits and slowly progressing motor symptoms and cognitive decline in mid to older adult ages. In addition, in some cases acute onset clinical deterioration led to a prolonged episode with reduced consciousness and even early death. Radiologically, pathognomonic changes are found at typical predilection sites involving the deep cerebral white matter sparing a periventricular and directly subcortical rim, the middle blade of corpus callosum, posterior limb of the internal capsule, middle cerebellar peduncles, cerebral peduncles and specifically the globus pallidus. Histopathologic characterization in two autopsy cases did not reveal angiopathy, but instead micro- to macrocystic degeneration of the white matter. Astrocytes were activated at early stages and later displayed severe degeneration and loss. In addition, despite the loss of myelin, elevated numbers of partly apoptotic oligodendrocytes were observed. A structural comparison of the variants in CST3 suggests that specific truncations of cystatin C result in an abnormal function, possibly by rendering the protein more prone to aggregation. Future studies are required to confirm the assumed effect on the protein and to determine pathophysiologic downstream events at the cellular level., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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26. BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis.
- Author
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Bergner CG, van der Meer F, Franz J, Vakrakou A, Würfel T, Nessler S, Schäfer L, Nau-Gietz C, Winkler A, Lagumersindez-Denis N, Wrzos C, Damkou IA, Sergiou C, Schultz V, Knauer C, Metz I, Bahn E, Rodriguez EG, Merkler D, Simons M, and Stadelmann C
- Abstract
Remyelination is a crucial regenerative process in demyelinating diseases, limiting persisting damage to the central nervous system (CNS). It restores saltatory nerve conduction and ensures trophic support of axons. In multiple sclerosis (MS) patients, remyelination has been observed in both white and grey matter and found to be more efficient in the cortex. Brain-enriched myelin-associated protein 1 (BCAS1) identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration. Other than in the white matter, BCAS1+ oligodendrocytes are maintained at high densities in the cortex throughout life. Here, we investigated cortical lesions in human biopsy and autopsy tissue from patients with MS in direct comparison to demyelinating mouse models and demonstrate that following a demyelinating insult BCAS1+ oligodendrocytes in remyelinating cortical lesions shift from a quiescent to an activated, internode-forming morphology co-expressing myelin-associated glycoprotein (MAG), necessary for axonal contact formation. Noteworthy, activated BCAS1+ oligodendrocytes are found at early time points of experimental demyelination amidst ongoing inflammation. In human tissue, activated BCAS 1+ oligodendrocytes correlate with the density of myeloid cells, further supporting their involvement in an immediate regenerative response. Furthermore, studying the microscopically normal appearing non demyelinated cortex in patients with chronic MS, we find a shift from quiescent BCAS1+ oligodendrocytes to mature, myelin-maintaining oligodendrocytes, suggesting oligodendrocyte differentiation and limited replenishment of BCAS1+ oligodendrocytes in long-standing disease. We also demonstrate that part of perineuronal satellite oligodendrocytes are BCAS1+ and contribute to remyelination in human and experimental cortical demyelination. In summary, our results provide evidence from human tissue and experimental models that BCAS1+ cells in the adult cortex represent a population of pre-differentiated oligodendrocytes that rapidly react after a demyelinating insult thus enabling immediate myelin regeneration. In addition, our data suggest that limited replenishment of BCAS1+ oligodendrocytes may contribute to the remyelination failure observed in the cortex in chronic MS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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