11163 research outputs found
Sort by
Epicardial adipose tissue as a prognostic parameter for patients with severe aortic valve stenosis and transfemoral catheter-based valve replacement
No full textIn dieser Arbeit wurde das EAT hinsichtlich seiner Bedeutung als prognostischer Parameter
für das Outcome nach TAVI bei Patient*innen mit schwerer AS beurteilt. Ein erhöhtes
EAT-Volumen war ein Prädiktor einer schlechteren Langzeitprognose, bei jedoch
identischer 30-Tages-Mortalität. Die schlechtere Prognose durch erhöhte EAT-Volumina
war unabhängig von Charakteristika der Aortenklappenstenose, der Subgruppe der
Aortenstenose und individuellen begleitenden kardiovaskulären Risikofaktoren. Innerhalb
einzelner Subgruppen der Aortenklappenstenose ermöglicht die nicht-invasive
Quantifizierung von EAT-Volumina keine verbesserte Risikostratifizierung.
Zusammenfassend untermauert diese Arbeit die Hypothese, dass ein erhöhtes EAT-
Volumen ein Marker eines höheren kardiovaskulären Risikoprofils und Morbidität darstellen
könnte und folglich als prognostischer Parameter für das langfristige Outcome nach TAVI
dienen könnte. Gleichermaßen ist es möglich das EAT-Volumen nicht-invasiv in
präinterventionellen Planungs-CTs zu quantifizieren, was eine einfache Anwendbarkeit in
der zukünftigen klinischen Routine erhoffen lässt.In this study, EAT was assessed in terms of its significance as a prognostic parameter
for the outcome after TAVI in patients with severe AS. An increased
EAT volume was a predictor of a poorer long-term prognosis, but with
identical 30-day mortality. The poorer prognosis associated with increased EAT volumes
was independent of the characteristics of aortic valve stenosis, the subgroup of
aortic stenosis, and individual concomitant cardiovascular risk factors. Within
individual subgroups of aortic valve stenosis, non-invasive
quantification of EAT volumes does not allow for improved risk stratification.
In summary, this study supports the hypothesis that increased EAT
volume could be a marker of a higher cardiovascular risk profile and morbidity
and could therefore serve as a prognostic parameter for long-term outcomes after TAVI
. Similarly, it is possible to quantify EAT volume non-invasively in
pre-interventional planning CT scans, which suggests that it could be easily applied in
future clinical routine.2026-04-0
Effect of selective estrogen and androgen receptor modulators on skeletal muscle in an orchiectomized rat model
No full textDie Sarkopenie ist eine altersassoziierte Erkrankung des Bewegungsapparats, die durch Immobilität, erhöhte Sturzneigung und häufigere Hospitalisierungen erheblich zur Belastung des Gesundheitssystems beiträgt. Aufgrund des demografischen Wandels nimmt ihre Bedeutung weiter zu. Ein wesentlicher ätiologischer Faktor ist der altersbedingte Mangel an Androgenen und Östrogenen. Männer sind in besonderem Maße betroffen, während wirksame therapeutische Optionen bislang fehlen. Ziel dieser Arbeit war die Untersuchung der Wirkung einer Kombinationstherapie aus dem selektiven Androgenrezeptormodulator (SARM) Ostarine und dem selektiven Östrogenrezeptormodulator (SERM) Raloxifen auf die Muskelstruktur im Modell der orchiektomierten Ratte.
Hierzu wurden acht Monate alte männliche Sprague-Dawley-Ratten bilateral orchiektomiert und in fünf Versuchsgruppen eingeteilt: eine nicht orchiektomierte Kontrollgruppe, eine unbehandelte orchiektomierte Gruppe sowie drei Therapiegruppen mit Ostarine, Raloxifen oder einer Kombination beider Substanzen. Die Behandlung erfolgte über 18 Wochen. Anschließend wurden die Skelettmuskeln gastrocnemius, soleus und longissimus histologisch untersucht. Analysiert wurden Muskelgewicht, Muskelfaserquerschnittsfläche und -durchmesser jeweils unter Berücksichtigung des Körpergewichts sowie Kerndichte und Kapillarisierung. Zusätzlich wurden die Gewichte der Prostata und des M. levator ani sowie ausgewählte Serumparameter bestimmt.
Die Orchiektomie führte zu einer Hormonmangelsituation mit reduziertem Körpergewicht sowie einer Abnahme der Gewichte von Prostata und M. levator ani. Ostarine zeigte einen anabolen Effekt auf den hormonsensiblen M. levator ani, war jedoch mit einem unerwünschten Effekt auf die Prostata assoziiert. Raloxifen führte zu einer Zunahme der körpergewichtskorrigierten Muskelfaserflächen und -durchmesser, was als Hinweis auf eine günstige Veränderung der fettfreien Körpermasse interpretiert wurde. Die Kombinationstherapie vereinte die Effekte beider Substanzen weitgehend und zeigte im Vergleich zur Ostarine-Monotherapie eine geringere Wirkung auf die Prostata.
Zusammenfassend zeigte insbesondere die Raloxifen-Monotherapie günstige Effekte auf die untersuchten Skelettmuskeln in Relation zum Körpergewicht. Die Ergebnisse deuten darauf hin, dass eine kombinierte pharmakologische Modulation von Androgen- und Östrogenrezeptoren einen potenziellen Ansatz zur Therapie der Sarkopenie beim Mann darstellen könnte, der jedoch in weiteren Studien validiert werden muss.Sarcopenia is an age-related musculoskeletal disorder that substantially contributes to the burden on healthcare systems through immobility, increased risk of falls, and frequent hospitalizations. Its prevalence is expected to rise further due to demographic changes. A key etiological factor is the age-related decline in androgen and estrogen levels. Men are particularly affected, while effective therapeutic options remain limited. The aim of this study was to investigate the effects of combination therapy with the selective androgen receptor modulator (SARM) ostarine and the selective estrogen receptor modulator (SERM) raloxifene on skeletal muscle structure in an orchiectomized rat model.
Eight-month-old male Sprague–Dawley rats were bilaterally orchiectomized and allocated to five experimental groups: a non-orchiectomized control group, an untreated orchiectomized group, and three treatment groups receiving ostarine, raloxifene, or a combination of both substances. Treatment was administered for 18 weeks. Subsequently, the gastrocnemius, soleus, and longissimus muscles were examined histologically. Muscle weight, muscle fiber cross-sectional area, and fiber diameter were analyzed with normalization to body weight, while nuclear density and capillarization were assessed independently. In addition, the weights of the prostate and levator ani muscle as well as selected serum parameters were determined.
Orchiectomy induced a hormone-deficient state characterized by reduced body weight and decreased weights of the prostate and levator ani muscle. Ostarine exerted an anabolic effect on the hormone-sensitive levator ani muscle but was associated with an undesirable effect on the prostate. Raloxifene treatment resulted in increased body weight–normalized muscle fiber cross-sectional areas and diameters, suggesting a favorable alteration in lean body mass. Combination therapy largely integrated the effects of both agents and showed a reduced impact on the prostate compared with ostarine monotherapy.
In conclusion, raloxifene monotherapy demonstrated particularly favorable effects on skeletal muscle parameters relative to body weight. These findings suggest that combined pharmacological modulation of androgen and estrogen receptors may represent a potential therapeutic approach for male sarcopenia, warranting further investigation.2026-03-3
The optimisation of methods to evaluate the impact of insecticides on non-target arthropods in forests
No full textInsect pests affect approximately 35 million hectares of forest globally each year. To mitigate tree mortality, insecticide treatments are employed as a last resort within the framework of Integrated Pest Management (IPM). Among these, large-scale aerial applications are a common strategy used to suppress insect-induced defoliation. However, public concerns remain—fuelled by negative historical experiences with insecticides, the global decline in insect populations, and discrepancies between the expected effects based on insecticide chemical properties and the effects observed in field studies. Additionally, many studies do not include statistical analyses at the species level, where unpredictable toxic effects are most likely to occur. This is because some species may exhibit ecological responses that deviate from patterns observed at higher taxonomic levels.
Conflicting study outcomes may result from logistical constraints that lead to methodological shortcomings. In parallel, the limited detection of species-level effects might be attributed to insufficient taxonomic expertise across various arthropod taxa. This thesis aims to identify and address these methodological flaws, which result in reporting inconsistencies, and to develop approaches for the effective application of DNA barcoding in such field trials.
Chapter 1 presents a systematic review evaluating study designs assessing the side effects of aerially applied insecticides on non-target forest arthropods. Specifically, we examined whether appropriate study designs yielded results consistent with the expected toxicological outcomes based on the insecticides’ chemical properties. We found that pseudoreplication was the primary cause of implausible results that contradicted these predictable toxic effects, and we provided guidance to ensure true replication in future studies.
Chapters 2 to 4 focus on optimizing DNA barcoding to support taxonomic identification. Chapter 2 (Stein et al. 2022) introduces a non-destructive DNA barcoding method that preserves specimens for morphological identification in cases where DNA barcoding fails. Chapter 3 (Stein et al. 2024) outlines a method for curating species assignments in the Barcode of Life Database (BOLD) to enhance DNA barcoding accuracy using sequence data and metadata, including morphological references and sampling locations. Chapter 4 (Stein and Gailing 2025) employs the curated record set from Stein et al. (2024) to identify systematic deficiencies in BOLD and proposes approaches to address them.
The results of this thesis indicate that pseudoreplication unduly fuels concerns about aerial insecticide applications in forests, while the optimized DNA barcoding methods developed here ensure the detection of unpredictable toxic effects at the species level. Moreover, sampling non-target arthropods plays a crucial role, as it bridges these two components. Without addressing both, field assessments of insecticides are likely to continue producing unreliable results, thereby compromising the scientific foundation of public debates surrounding aerially applied insecticides in forest ecosystems. Such public concerns may paradoxically delay the development and authorization of forthcoming, highly specific RNA silencing-based insecticides.2026-02-0
Optimization in Nonlinear Spaces
No full textFixed point iterations constructed from proximal mappings have been extensively studied on linear spaces, yielding various local and global convergence results. We develop a theory for α-firmly nonexpansive fixed point mappings in p-uniformly convex and CAT(k) metric spaces. A central achievement is the analysis of proximal point algorithms in positively curved spaces, a setting where standard arguments from nonpositively curved spaces no longer apply. Our algorithms achieve local linear convergence under the assumption of linear metric subregularity.
Complementary to the algorithmic analysis, proximal mappings again play a central role as we develop a symbolic computational framework for monotone operators and subdifferentials on the real line. Within this framework, we focus on a class of monotone operators that is well suited for symbolic representation and manipulation in computer algebra systems. This class admits a natural correspondence with subdifferentials of a suitable family of convex functions, and proximal mappings, subdifferentials, and Fenchel conjugates provide the links between the classes.2026-02-2
Bypass von mRNA-Qualitätskontrolle generiert aberrante EYA1-Isoform in tumorassoziierten Fibroblasten des Pankreas-CA
No full textEYA1 plays a key role in the embryonic development of various organs. Further, it has a profibrotic effect, thus influencing the pathogenesis of various diseases and malignancies. Its tyrosine phosphatase activity and initiation of DNA repair mechanisms have been identified as driving factors for the profibrotic effect. Exon-array datasets have shown that EYA1 undergoes alternative splicing in different parenchymal organs, leading to the formation of various EYA1 isoforms. Alternative splicing affects the phosphatase activity of individual EYA1 isoforms and thus also their profibrotic effect. In samples from pancreatic ductal adenocarcinoma (PDAC), which is characterized by its destructive, fibrotic organ remodeling, an aberrant EYA1 splice variant called EYA1A∆e11 was identified, characterized by the loss of exon 11. For the first time, this study reports the detection of this aberrant splice variant at the protein level via western blot, both in vitro and in vivo. At the same time, a decrease in the normal variant, which predominantly appears in healthy pancreatic tissue, was observed. Additionally, EYA1A∆e11 was described as a stress-induced transcript in tumor tissue as well as isolated tumor-associated fibroblasts.
Epigenetic modifications play a crucial role in gene activation and protein biosynthesis. The oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (hmrC) in mRNA, catalyzed by the TET3 oxygenase, enables rapid translation of transcripts. This thesis demonstrates that cellular stress induces an increase in the expression and a simultaneous cytoplasmic shift of TET3 in PDAC, which is associated with a concomitant rise in hmrC. The detection of RNA modification was also achieved via dot blot in tumor-associated fibroblasts. This may explain the faster and enhanced expression of stress-induced transcripts such as EYA1A∆e11 and underscores the assumption that TET3 does not function as a tumor suppressor gene, as was long assumed.2026-03-0
Application of large-scale sequence data in dairy cattle genomics
No full textModern genomic methods such as genotyping and sequencing, enhanced with biostatistical
approaches like imputation have provided insight into the genetic architecture of traits of economic
importance, as well as the traits associated with animal health. These traits often have a complex
nature, with many variants of small effects that impact the trait expression. To associate the effect
of the variant with a trait of interest, genome-wide association studies (GWAS) have been
developed. Despite the success of GWAS in the identification of candidate genes and regions,
causal variants in dairy cattle are still mostly unknown. To be able to capture the possible
association of a variant on a trait, and get more insight into genetic architecture, large samples are
usually needed. Another complication is the existence of long linkage disequilibrium (LD) in
cattle, which makes it challenging to decipher the true association between a variant and a trait.
Post-GWAS analyses that help reveal the true association such as fine-mapping and functional
annotation using the external information about the variant’s function have been implemented
lately. These will become even more important in the future, with ever-increasing sample sizes,
leading to the discovery of more associations, to prioritize the large number of significant
associations obtained through GWAS. In this work, I aimed to infer the novel trait-specific and
trait-shared variants and genes associated with 36 complex traits of substantial economic and
health importance in German Holstein, the most important dairy breed worldwide.
The general introduction Chapter 1 starts with the history of cattle domestication and selection
and describes how these impacted cattle’s LD and effective population size. This is continued with
a discussion on breeding goals in modern dairy cattle breeding with specific attention on the
German Holstein breed. The current state of knowledge of GWAS and the use of genotype and
sequence data in dairy cattle genomics are further described. Finally, the application of GWAS
follow-up methods such as fine-mapping and functional annotation are discussed. This thesis
consists of three manuscripts that are presented in Chapters 2, 3, and 4. Chapter 2 describes the
imputation of 180,217 German Holstein cows to sequence level, and subsequent GWAS for milk,
fat, and protein yield – one of the most important traits in dairy cattle breeding. I also present
Bayesian-based fine-mapping of genome-wide significant signals and subsequent functional
annotation using the external multi-omics information about the variant’s function. The use of
large-scale GWAS in our study led to the identification of tens of thousands of significant variants,
across all traits. With fine-mapping, I prioritized the potential causal variants among all significant
signals, and with functional annotation further narrowed down the potential causal signals.
Eventually, genetic variance explained by novel candidate variants was estimated, leading to the
unique list of variants with a high potential for causality. Additionally, I present the computational
challenges faced when dealing with large datasets and assess the performance of different GWAS
software. Lately, more emphasis has been put on animal health and traits addressing them. These
were often neglected in the past when breeding goals were oriented toward production exclusively.
Consequently, these declined due to intense selection for milk yield over the years. To research
the genetic architecture of the most common diseases in cattle, in Chapter 3 I present the GWAS
and Bayesian fine-mapping results of 11 health traits that are part of today’s balanced breeding
goal in Germany. Large numbers of novel candidate variants and genes were discovered, of which
many were in common across 11 researched traits, as well as with other non-researched traits,
presenting the opportunity for inclusion in selection programs on different health traits. Chapter
4 reports the findings of a huge meta-analysis of health and conformation traits in hundreds of
thousands of cows, leading to the discovery of shared genomic regions between different traits and
groups of traits. This is important for multiple breeding scheme goals, as the majority of the
breeding programs nowadays are conceived in a way that they take different groups of traits
including animal health, conformation, fertility, and production into account. Finally, in Chapter
5 I evaluate the findings from the manuscripts presented in Chapters 2, 3, and 4 and propose their
potential application in modern dairy cattle breeding. Since the biggest advantage of our study
which led to the discovery of new associations was the size of the datasets, I also discuss the merits
and challenges when working with large data, in both computational and data evaluation ways.2026-03-1
Super-Resolution Imaging Approaches To Determine The Organization of B Lymphocyte Surface Receptors
No full textThis thesis presents a multidisciplinary investigation into B cell membrane biology andnanobody-based molecular targeting, spanning the development of new imaging techniques,a novel nanobody discovery platform, and functional validation of therapeutic candidates.Across three chapters, I address fundamental questions in B cell receptor (BCR) signaling,present a novel nanobody discovery technique for membrane proteins, and translationallyapply these nanobodies for immunotherapy. In Chapter 1, I aim to examine a long-standingdebate regarding the nanoscale organization and activation mechanism of BCRs. To addresslimitations in imaging suspended B cells, I developed a novel “Membrane Sheet PressingMethod (MSPM)” technique to generate high-quality membrane sheets, which I combinedwith super-resolution microscopy and stoichiometric labelling using specific monovalentnanobodies. This enabled us to have an accurate estimation of BCR organization across largesurface areas. Using engineered cell lines with specific BCRs and antigens of defined valency,we demonstrated that BCR clustering size is the primary trigger for signaling, rather thanantigen binding or antigen valency alone, and that BCR-cluster size acts as a threshold foractivation. In Chapter 2, I introduce Reverse Phage Display (RPD), a method that invertstraditional nanobody selection by identifying binders to native membrane proteins withoutprior knowledge of the target. RPD overcomes challenges of high failure rate for membraneproteins, recombinant antigen production, and antigen conformation loss, and uniquelyenables the discovery of previously unknown or poorly characterized surface proteins,including those relevant to cancer, a key feature that classical display methods lack. Using thisapproach, I discovered nanobodies against CD45, surface IgM, and CD38, along with severalcandidates still under investigation. Notably, two of the selected nanobodies resulted not onlyin high specificity, but with strong affinities in the low picomolar range, highlighting theplatform’s stringency and precision. In Chapter 3, I focus on CD38 as a therapeutic target. Icharacterize NbC6, a nanobody with superior affinity and a unique epitope profile, capable ofoutperforming FDA-approved therapeutic antibodies Daratumumab and Isatuximab in keyassays. Together, in this thesis I perform nanoscale B cell membrane analysis, rapid nanobodydiscovery, and translational antibody engineering.2026-07-0
Analysis of small nucleolar (sno)RNA shuttling in Saccharomyces cerevisiae
No full textSmall nucleolar (sno)RNAs are a group of non-coding RNAs and can be classified into box C/D snoRNA and box H/ACA snoRNA based on their conserved sequences. They are further associated with snoRNA core proteins to form ribonucleoprotein complexes. The main function of snoRNPs is the post-transcriptional modification of rRNA. After transcription, the pre-snoRNAs are usually terminated by the Nrd1-Nab3-Sen1 (NNS) complex, followed by the core protein assembly and the 3’- and 5’-end processing. Finally, the mature snoRNPs are translocated to the nucleolus to fulfill their function. The whole biogenesis of snoRNA has been thought to occur exclusively in the nucleus. Recent studies suggest that some snoRNAs might be exported into the cytoplasm. However, it remained unclear for what reason they shuttle between the nucleus and the cytoplasm. This study used baker’s yeast Saccharomyces cerevisiae to analyze the shuttling. We show that some pre-snoRNAs are exported via Mex67. Moreover, we demonstrate that the transcription termination determines whether a pre-snoRNA is exported. Some snoRNAs contain a bipartite terminator and can therefore be alternatively terminated by the cleavage and polyadenylation (CPF-CF) complex as a fail-safe pathway. When the major NNS termination pathway is used, maturation takes place in the nucleus. We carried out systematic studies with the snoRNA snR13 in which we mutated the binding site of the NNS complex. When the CPF-CF pathway is preferentially used upon insertion of the NNS-mutation, the pre-snoRNA is polyadenylated and bound by Lhp1 and several mRNA guard proteins, such as Nab2 and Hrp1. These proteins recruit the export receptor Mex67 to facilitate the nuclear export. In the cytoplasm, Lhp1 and the Lsm2-8 ring, which are loaded onto the pre-snoRNA in the nucleus, protect the pre-snoRNA, until the Lsm2-8 ring recruits the import receptors Cse1 and Mtr10 for nuclear re-import. The assembly of the core proteins occurs partially after the re-import. Subsequently, final processing at both 3’- and 5’-ends proceeds to generate a mature snoRNP. Importantly, the CPF-CF terminated snoRNAs are fully functional to conduct the respective rRNA modifications. In conclusion, this study provides new insights into the snoRNA maturation and its shuttling.2026-06-2
Microglia Along Anatomical Pathways in Relation to Neuropathological Changes in Alzheimer's Disease
No full textAlzheimer’s disease (AD) is a neurodegenerative disorder characterised by complex protein and cellular pathology. This study investigated the densities and spatial correlations of amyloid-β (Aβ), hyperphosphorylated tau (h-tau), ramified microglia, and somatostatin-positive (SOM+) interneurons across three brain regions: the lateral geniculate nucleus (LGN), primary visual cortex (V1) and the subiculum/the CA4 of the hippocampus in postmortem tissue from 36 individuals. Immunohistochemistry and digital density analysis (n/mm²) were used to quantify markers and assess their relationships across AD stages.
Findings of this study assessed the occurence of said protein and cell types in the three brain regions. Amongst the noteworthy results, significant AT8 and 6E10 immunoreactivity was observed in the LGN, indicating early h-tau and Aβ aggregation. Notably, LGN AT8+ reactivity, interpreted as seed-competent tau, correlated with AD-pathology in V1, supporting transneuronal spread. Microglial analysis revealed a significant reduction in ramified microglia density in the subiculum relative to the LGN in high tangle burden cases, highlighting region-specific microglial responses. SOM+ interneurons, found only in CA4 and V1, showed a non-significant trend toward reduced density with advancing AD but no correlations with microglia or protein aggregates. These findings offer novel insights into the spatiotemporal dynamics of AD pathology and underscore the need for further investigation into regional vulnerabilities and intercellular interactions.2026-07-3
In vivo modelling of human central nervous system disease using chimeric mice
No full textX-linked adrenoleukodystrophy (X-ALD) is a monogenic peroxisomal disorder caused by loss of function mutations in the ABCD1 gene, leading to impaired β-oxidation of very long-chain fatty acids (VLCFAs) and their pathological accumulation in plasma and tissues. The most devastating clinical manifestation, cerebral adrenoleukodystrophy (cALD), primarily affects boys before puberty and presents as a rapidly progressive neurodegenerative syndrome. This disease phenotype is characterized histopathologically by inflammatory demyelination and extensive axonal injury.
Despite detailed pathological descriptions, the initiating cellular events and the mechanisms that drive lesion progression remain poorly defined. Prior histopathological analyses, including from our lab, suggested that early microglial loss may precede and potentially trigger lesion formation. Building on this, I hypothesized that integrating markers of microglial activation could refine lesion staging by more precisely capturing microglial dynamics. I identified an upregulation of GPNMB - a canonical damage-associated microglial protein - within actively demyelinating lesions in cALD autopsy specimens. Conversely, the interferon-stimulated gene MX1 was elevated both in histologically normal-appearing white matter (NAWM) and again at a later lesion stage, characterized by abundant foamy macrophages. These findings implicate type I interferon signalling as a potential early molecular signature associated with heightened susceptibility to cerebral inflammatory conversion in X-ALD.
Current murine models of X-ALD fail to recapitulate the inflammatory demyelinating phenotype and lack microglial depletion. To better model the human disease context, I developed a xenotransplantation-compatible mouse system that enables the engraftment of human induced pluripotent stem cell (hiPSC)-derived hematopoietic progenitor cells (HPCs) at any developmental stage. This approach results in stable, long-term repopulation of the mouse central nervous system (CNS) with human microglia-like cells (hMLCs) and CNS-associated macrophages (hCAMs). Single-cell RNA sequencing confirmed a homeostatic transcriptional profile of hMLCs, including canonical microglial genes P2RY12, TMEM119, CX3CR1, and SALL1. Functionally, hMLCs responded robustly to laser-induced injury in intravital two-photon microscopy and exhibited efficient phagocytosis following lysophosphatidylcholine (LPC)-induced focal demyelination in the murine corpus callosum.
Recognizing that X-ALD is unlikely to be a microglia-intrinsic disorder, I established a tri-cellular human CNS chimeric model encompassing human MLCs, astrocytes, and neurons. This platform enables the dissection of human glial-neuronal interactions under physiological and pathological conditions.
To further model X-ALD in vitro, I generated and characterized an ABCD1-deficient iPSC line that retained pluripotency and exhibited VLCFA accumulation - the biochemical hallmark of X-ALD - across multiple lineages. Co-culture experiments revealed that ABCD1-deficient astrocytes failed to potentiate microglial phagocytosis and cytokine secretion, in contrast to ABCD1-competent controls, suggesting a non-cell-autonomous impairment in microglial activation.
Together, this work provides novel mechanistic insights into the cellular orchestration of cALD lesion evolution, establishes a robust in vivo platform for long-term human glial studies, and offers experimental tools to interrogate multicellular neuroinflammatory processes in X-ALD and related disorders.2026-06-2