IF 5.4 2区医学

Glia Pub Date : 2024-12-24 DOI: 10.1002/glia.24662

Catharina Donkels, Ute Häussler, Susanne Huber, Nina Tiesmeyer, Theo Demerath, Christian Scheiwe, Mukesch J Shah, Marcel Heers, Horst Urbach, Andreas Schulze-Bonhage, Marco Prinz, Andreas Vlachos, Jürgen Beck, Julia M Nakagawa, Carola A Haas

{"title":"Dysregulation of Myelination in Focal Cortical Dysplasia Type II of the Human Frontal Lobe.","authors":"Catharina Donkels, Ute Häussler, Susanne Huber, Nina Tiesmeyer, Theo Demerath, Christian Scheiwe, Mukesch J Shah, Marcel Heers, Horst Urbach, Andreas Schulze-Bonhage, Marco Prinz, Andreas Vlachos, Jürgen Beck, Julia M Nakagawa, Carola A Haas","doi":"10.1002/glia.24662","DOIUrl":"https://doi.org/10.1002/glia.24662","url":null,"abstract":"Focal cortical dysplasias (FCDs) are local malformations of the human neocortex and a leading cause of intractable epilepsy. FCDs are classified into different subtypes including FCD IIa and IIb, characterized by a blurred gray-white matter boundary or a transmantle sign indicating abnormal white matter myelination. Recently, we have shown that myelination is also compromised in the gray matter of FCD IIa of the temporal lobe. Since myelination is key for brain function, which is imbalanced in epilepsy, in the current study, we investigated myelination in the gray matter of FCD IIa and IIb from the frontal lobe on the morphological, ultrastructural, and transcriptional level. We found that FCD IIa presents with an ordinary radial myelin fiber pattern, but with a reduced thickness of myelin sheaths of 500-1000 nm thick axons in comparison to FCD IIb and with an attenuation of the myelin synthesis machinery. In contrast, FCD IIb showed an irregular and disorganized myelination pattern covering an enlarged area in comparison to FCD IIa and controls and with increased numbers of myelinating oligodendrocytes (OLs). FCD IIb had significantly thicker myelin sheaths of large caliber axons (above 1000 nm) when compared to FCD IIa. Accordingly, FCD IIb showed a significant up-regulation of myelin-associated mRNAs in comparison to FCD IIa and enhanced binding capacities of the transcription factor MYRF to target sites in myelin-associated genes. These data indicate that FCD IIa and IIb are characterized by a differential dysregulation of myelination in the gray matter of the frontal lobe.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Image, Volume 73, Issue 2

IF 5.4 2区医学

Glia Pub Date : 2024-12-21 DOI: 10.1002/glia.24546

Maria Gotkiewicz, Janne Capra, Pasi O. Miettinen, Teemu Natunen, Heikki Tanila

引用次数: 0

Cover Image, Volume 73, Issue 1 封面图片，第 73 卷第 1 期

IF 5.4 2区医学

Glia Pub Date : 2024-12-20 DOI: 10.1002/glia.24544

Maria Gotkiewicz, Janne Capra, Pasi O. Miettinen, Teemu Natunen, Heikki Tanila

引用次数: 0

WDR49-Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration and Alzheimer's Disease. wdr49阳性星形胶质细胞标志着额颞叶变性和阿尔茨海默病神经退行性变的严重程度

IF 5.4 2区医学

Glia Pub Date : 2024-12-20 DOI: 10.1002/glia.24663

Ana Rajicic, Lucia A A Giannini, Emma Gerrits, Renee van Buuren, Shamiram Melhem, Johan A Slotman, Annemieke J M Rozemuller, Bart J L Eggen, John C van Swieten, Harro Seelaar

{"title":"WDR49-Positive Astrocytes Mark Severity of Neurodegeneration in Frontotemporal Lobar Degeneration and Alzheimer's Disease.","authors":"Ana Rajicic, Lucia A A Giannini, Emma Gerrits, Renee van Buuren, Shamiram Melhem, Johan A Slotman, Annemieke J M Rozemuller, Bart J L Eggen, John C van Swieten, Harro Seelaar","doi":"10.1002/glia.24663","DOIUrl":"https://doi.org/10.1002/glia.24663","url":null,"abstract":"A subpopulation of astrocytes expressing WD Repeat Domain 49 (WDR49) was recently identified in frontotemporal lobar degeneration (FTLD) with GRN pathogenic variants. This is the first study to investigate their expression and relation to pathology in other FTLD subtypes and Alzheimer's disease (AD). In a postmortem cohort of TDP-43 proteinopathies (12 GRN, 11 C9orf72, 9 sporadic TDP-43), tauopathies (13 MAPT, 8 sporadic tau), 10 AD, and four controls, immunohistochemistry and immunofluorescence were performed for WDR49 and pathological inclusions on frontal, temporal, and occipital cortical sections. WDR49-positive cell counts (adjusted per mm2) were examined and related to digitally quantified percentage areas of TDP-43/tau pathology and semiquantitative scores of neurodegeneration. Quantitative colocalization analysis of WDR49 and pathological inclusions was done. WDR49-positive astrocytes were present across FTLD subtypes and AD in the brain parenchyma and (peri-)vascular space, with distinct morphological patterns, and were particularly enriched in gray matter. In controls, sporadic WDR49-positive cells were found enveloping vessels. WDR49-positive astrocytes were most abundant in the frontal cortex (FC) of GRN cases and temporal cortex in GRN, AD, and sporadic primary tauopathy. In the occipital cortex, only a few cells were found across groups. WDR49-positive astrocyte counts positively correlated with the severity of neurodegeneration and TDP-43 pathology but not tauopathy. Furthermore, in frontotemporal cortices, WDR49 partly colocalized with TDP-43 (14%-21%) and tau (31%-45%). In conclusion, WDR49 is a marker for a subset of astrocytes with different morphologies across FTLD and AD, reflecting the severity of neurodegeneration. These astrocytes may become activated in neurodegeneration in response to pathological damage and migrate from the vessel wall to the parenchyma.","PeriodicalId":174,"journal":{"name":"Glia","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Axonal Selectivity of Myelination by Single Oligodendrocytes Established During Development in Mouse Cerebellar White Matter 小鼠小脑白质发育过程中形成的单个少突胶质细胞髓鞘化的轴突选择性

IF 5.4 2区医学

Glia Pub Date : 2024-12-17 DOI: 10.1002/glia.24660

Batpurev Battulga, Yasuyuki Osanai, Reiji Yamazaki, Yoshiaki Shinohara, Nobuhiko Ohno

{"title":"Axonal Selectivity of Myelination by Single Oligodendrocytes Established During Development in Mouse Cerebellar White Matter","authors":"Batpurev Battulga, Yasuyuki Osanai, Reiji Yamazaki, Yoshiaki Shinohara, Nobuhiko Ohno","doi":"10.1002/glia.24660","DOIUrl":"10.1002/glia.24660","url":null,"abstract":"Myelin formation by oligodendrocytes regulates the conduction velocity and functional integrity of neuronal axons. While individual oligodendrocytes form myelin sheaths around multiple axons and control the functions of neural circuits where the axons are involved, it remains unclear if oligodendrocytes selectively form myelin sheaths around specific subtypes of axons. Using the combination of rabies virus-mediated single oligodendrocyte labeling and immunostaining with tissue clearing, we revealed that approximately half of the oligodendrocytes preferentially myelinate axons originating from Purkinje cells in the white matter of adult mouse cerebella. The preference for Purkinje cell axons was more pronounced during development when the process of myelination within cerebellar white matter was initiated; over 90% of oligodendrocytes preferentially myelinated Purkinje cell axons. Preferential myelination of Purkinje cell axons was further confirmed by immuno-electron microscopy and transgenic mice that label early-born oligodendrocytes. Transgenic mice that label oligodendrocytes differentiated at the early development showed that early-born oligodendrocytes preferentially myelinate Purkinje cell axons in the matured cerebellar white matter. In contrast, transgenic mice that label oligodendrocytes differentiated after the peak of cerebellar myelination showed that the later-differentiated oligodendrocytes dominantly myelinated non-Purkinje cell axons. These results demonstrate that a significant proportion of oligodendrocytes preferentially myelinate functionally distinct axons in the cerebellar white matter, and the axonal preference of myelination by individual oligodendrocytes is established depending on the timing of their differentiation during development. Our data provide the evidence that there is a critical time window of myelination that a specific subtype of axons are dominantly myelinated by the oligodendrocytes.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 4","pages":"873-886"},"PeriodicalIF":5.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lipids: Emerging Players of Microglial Biology 脂质：小胶质细胞生物学的新角色

IF 5.4 2区医学

Glia Pub Date : 2024-12-17 DOI: 10.1002/glia.24654

Priya Prakash, Caitlin E. Randolph, Katherine A. Walker, Gaurav Chopra

{"title":"Lipids: Emerging Players of Microglial Biology","authors":"Priya Prakash, Caitlin E. Randolph, Katherine A. Walker, Gaurav Chopra","doi":"10.1002/glia.24654","DOIUrl":"10.1002/glia.24654","url":null,"abstract":"Lipids are small molecule immunomodulators that play critical roles in maintaining cellular health and function. Microglia, the resident immune cells of the central nervous system, regulate lipid metabolism both in the extracellular environment and within intracellular compartments through various mechanisms. For instance, glycerophospholipids and fatty acids interact with protein receptors on the microglial surface, such as the Triggering Receptor Expressed on Myeloid Cells 2, influencing cellular functions like phagocytosis and migration. Moreover, cholesterol is essential not only for microglial survival but, along with other lipids such as fatty acids, is crucial for the formation, function, and accumulation of lipid droplets, which modulate microglial activity in inflammatory diseases. Other lipids, including acylcarnitines and ceramides, participate in various signaling pathways within microglia. Despite the complexity of the microglial lipidome, only a few studies have investigated the effects of specific lipid classes on microglial biology. In this review, we focus on major lipid classes and their roles in modulating microglial function. We also discuss novel analytical techniques for characterizing the microglial lipidome and highlight gaps in current knowledge, suggesting new directions for future research on microglial lipid biology.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 3","pages":"657-677"},"PeriodicalIF":5.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alzheimer's Disease Risk Gene SORL1 Promotes Receptiveness of Human Microglia to Pro-Inflammatory Stimuli 阿尔茨海默病风险基因SORL1促进人类小胶质细胞对促炎刺激的接受性

IF 5.4 2区医学

Glia Pub Date : 2024-12-17 DOI: 10.1002/glia.24659

Peter Lund Ovesen, Kristian Juul-Madsen, Narasimha S. Telugu, Vanessa Schmidt, Silke Frahm, Helena Radbruch, Emma Louise Louth, Anders Rosendal Korshøj, Frank L. Heppner, Sebastian Diecke, Helmut Kettenmann, Thomas E. Willnow

{"title":"Alzheimer's Disease Risk Gene SORL1 Promotes Receptiveness of Human Microglia to Pro-Inflammatory Stimuli","authors":"Peter Lund Ovesen, Kristian Juul-Madsen, Narasimha S. Telugu, Vanessa Schmidt, Silke Frahm, Helena Radbruch, Emma Louise Louth, Anders Rosendal Korshøj, Frank L. Heppner, Sebastian Diecke, Helmut Kettenmann, Thomas E. Willnow","doi":"10.1002/glia.24659","DOIUrl":"10.1002/glia.24659","url":null,"abstract":"Sorting protein-related receptor containing class A repeats (SORLA) is an intracellular trafficking receptor encoded by the Alzheimer's disease (AD) gene SORL1 (sortilin-related receptor 1). Recent findings argue that altered expression in microglia may underlie the genome-wide risk of AD seen with some SORL1 gene variants, however, the functional significance of the receptor in microglia remains poorly explained. Using unbiased omics and targeted functional analyses in iPSC-based human microglia, we identified a crucial role for SORLA in sensitizing microglia to pro-inflammatory stimuli. We show that SORLA acts as a sorting factor for the pattern recognition receptor CD14, directing CD14 exposure on the cell surface and priming microglia to stimulation by pro-inflammatory factors. Loss of SORLA in gene-targeted microglia impairs proper CD14 sorting and blunts pro-inflammatory responses. Our studies indicate an important role for SORLA in shaping the inflammatory brain milieu, a biological process important to local immune responses in AD.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 4","pages":"857-872"},"PeriodicalIF":5.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi Layered Omics Approaches Reveal Glia Specific Alterations in Alzheimer's Disease: A Systematic Review and Future Prospects 多层组学方法揭示阿尔茨海默病中胶质细胞特异性改变：系统回顾和未来展望。

IF 5.4 2区医学

Glia Pub Date : 2024-12-09 DOI: 10.1002/glia.24652

Özkan İş, Yuhao Min, Xue Wang, Stephanie R. Oatman, Ann Abraham Daniel, Nilüfer Ertekin-Taner

{"title":"Multi Layered Omics Approaches Reveal Glia Specific Alterations in Alzheimer's Disease: A Systematic Review and Future Prospects","authors":"Özkan İş, Yuhao Min, Xue Wang, Stephanie R. Oatman, Ann Abraham Daniel, Nilüfer Ertekin-Taner","doi":"10.1002/glia.24652","DOIUrl":"10.1002/glia.24652","url":null,"abstract":"Alzheimer's disease (AD) is the most common neurodegenerative dementia with multi-layered complexity in its molecular etiology. Multiple omics-based approaches, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and lipidomics are enabling researchers to dissect this molecular complexity, and to uncover a plethora of alterations yielding insights into the pathophysiology of this disease. These approaches reveal multi-omics alterations essentially in all cell types of the brain, including glia. In this systematic review, we screen the literature for human studies implementing any omics approach within the last 10 years, to discover AD-associated molecular perturbations in brain glial cells. The findings from over 200 AD-related studies are reviewed under four different glial cell categories: microglia, oligodendrocytes, astrocytes and brain vascular cells. Under each category, we summarize the shared and unique molecular alterations identified in glial cells through complementary omics approaches. We discuss the implications of these findings for the development, progression and ultimately treatment of this complex disease as well as directions for future omics studies in glia cells.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 3","pages":"539-573"},"PeriodicalIF":5.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potassium Release From the Habenular Astrocytes Induces Depressive-Like Behaviors in Mice 小鼠缰状星形胶质细胞释放钾诱导抑郁样行为。

IF 5.4 2区医学

Glia Pub Date : 2024-11-29 DOI: 10.1002/glia.24647

Hidenori Aizawa, Miho Matsumata, Laura Ayaka Noguera Oishi, Fumie Nishimura, Deepa Kamath Kasaragod, Xintong Yao, Wanqin Tan, Tomomi Aida, Kohichi Tanaka

{"title":"Potassium Release From the Habenular Astrocytes Induces Depressive-Like Behaviors in Mice","authors":"Hidenori Aizawa, Miho Matsumata, Laura Ayaka Noguera Oishi, Fumie Nishimura, Deepa Kamath Kasaragod, Xintong Yao, Wanqin Tan, Tomomi Aida, Kohichi Tanaka","doi":"10.1002/glia.24647","DOIUrl":"10.1002/glia.24647","url":null,"abstract":"The habenula has been implicated in psychiatric disorders such as depression, primarily because of its role in the modulation of the dopaminergic and serotonergic systems, which play a role in the pathophysiology of these disorders. Despite growing evidence supporting the role of the habenula in behavioral regulation, the process by which neural cells develop in the habenula remains elusive. Since the habenular anlage is found in the prosomere 2 domain expressing transcription factor Dbx1 in mouse embryos, we hypothesized that the Dbx1-expressing prosomere domain is a source of astrocytes that modulate neuronal activity in the habenula. To address this, we examined the cell lineage generated from Dbx1-expressing cells in male mice using tamoxifen-inducible Cre recombinase under the control of the Dbx1 promoter. Perinatal induction of Cre activity labeled cells migrating radially from the ventricular zone to the pial side of the habenular anlage, and eventually showed astrocyte-like morphology with expression of the marker protein, S100β, for mature astrocytes in the habenula of the adult mouse. Photostimulation of astrocytes expressing ChR2 released potassium ions into the extracellular space, which in turn excited the neurons with an increased firing rate in the lateral habenula. Finally, photostimulation of habenular astrocytes exacerbated depression-like phenotypes with reduced locomotor activity, exaggerated despair behavior and impaired sucrose preference in open-field, tail suspension and sucrose preference tests, respectively. These results indicated that the Dbx1-expressing perinatal domain generated astrocytes that modulated neuronal activity via the regulation of extracellular potassium levels.","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 4","pages":"759-772"},"PeriodicalIF":5.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.24647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic Potential of Growth Hormone in Peripheral Nerve Injury: Enhancing Schwann Cell Proliferation and Migration Through IGF-1R-AKT and ERK Signaling Pathways 生长激素在周围神经损伤中的治疗潜力：通过IGF-1R-AKT和ERK信号通路促进雪旺细胞增殖和迁移。

IF 5.4 2区医学

Glia Pub Date : 2024-11-28 DOI: 10.1002/glia.24653

Jiaqian Chen, Tingcheng Zhang, Chaohu Wang, Peirong Niu, Liehao Huang, Rongrong Guo, Chengdong Wu, Huarong Zhang, Zhiyong Wu, Songtao Qi, Yi Liu

{"title":"Therapeutic Potential of Growth Hormone in Peripheral Nerve Injury: Enhancing Schwann Cell Proliferation and Migration Through IGF-1R-AKT and ERK Signaling Pathways","authors":"Jiaqian Chen, Tingcheng Zhang, Chaohu Wang, Peirong Niu, Liehao Huang, Rongrong Guo, Chengdong Wu, Huarong Zhang, Zhiyong Wu, Songtao Qi, Yi Liu","doi":"10.1002/glia.24653","DOIUrl":"10.1002/glia.24653","url":null,"abstract":"<div>\u0000 \u0000 Peripheral nerve injury (PNI) represents a prevalent condition characterized by the demyelination of affected nerves. The challenge of remyelinating these nerves and achieving satisfactory functional recovery has long been a persistent issue. The specific contributions of growth hormone (GH) in the aftermath of PNI have remained ambiguous. Our investigations have demonstrated that GH not only enhances neurological function scores but also promotes remyelination within a three-week period. Further in vivo studies corroborated that GH facilitates nerve function improvement by mitigating neuronal apoptosis. In vitro, the ideal concentration of GH for exerting effects on Schwann cells (SCs) has been identified as 80 ng/mL. Subsequent research uncovered GH's profound impact on SCs proliferation, cell cycle progression, and migration. Through RNA sequencing and additional experiments, it was discovered that GH treatment elevates the phosphorylation levels of IGF-1R, AKT, and ERK. Moreover, the GH-induced proliferation and migration of SCs were significantly diminished by the inhibition of the IGF-1R pathway, achieved through pre-treatment with Linsitinib. The outcomes of this investigation suggest that GH can significantly enhance the proliferation and migration of SCs, presenting it as a viable option for PNI repair.\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"73 4","pages":"805-821"},"PeriodicalIF":5.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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