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  1. AU="Krumm, Laura"
  2. AU="Shimura, Hidetoshi"
  3. AU="Munguia-Lopez, Jose Gil"
  4. AU="Eysert, Fanny"
  5. AU="Qazi Arisa, Fakhar Ali"
  6. AU="Guan, Yunshan"
  7. AU="Ayachi, Jihene"
  8. AU="Boulvard Chollet, Xavier L E"
  9. AU="Kwon, Sohee"
  10. AU=Fra-Bido Sigrid
  11. AU="Delgado, Teresa Cardoso"
  12. AU="Judy Ly"
  13. AU="E Richtig"
  14. AU="Jones, D. C."
  15. AU="Revillet, Hélène" AU="Revillet, Hélène"
  16. AU="Lee, Ji Ye"
  17. AU="Yoshinaga, Kazuaki"
  18. AU="Moturi, Krishna"
  19. AU="Loizeau, J"
  20. AU="Gentry, Matthew S"
  21. AU="Drury, Lucy S"
  22. AU="Caraman, Irina"

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  1. Artikel ; Online: Plasma Neurofilaments: Potential Biomarkers of SPG11-Related Hereditary Spastic Paraplegia.

    Krumm, Laura / Winkler, Jürgen / Winner, Beate / Regensburger, Martin

    Movement disorders : official journal of the Movement Disorder Society

    2024  Band 39, Heft 4, Seite(n) 755–757

    Mesh-Begriff(e) Humans ; Spastic Paraplegia, Hereditary/genetics ; Spastic Paraplegia, Hereditary/blood ; Spastic Paraplegia, Hereditary/diagnosis ; Biomarkers/blood ; Male ; Adult ; Female ; Neurofilament Proteins/blood ; Proteins/genetics ; Middle Aged
    Chemische Substanzen SPG11 protein, human ; Biomarkers ; Neurofilament Proteins ; Proteins
    Sprache Englisch
    Erscheinungsdatum 2024-02-21
    Erscheinungsland United States
    Dokumenttyp Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 607633-6
    ISSN 1531-8257 ; 0885-3185
    ISSN (online) 1531-8257
    ISSN 0885-3185
    DOI 10.1002/mds.29755
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2555: Hefte anzeigen Standort:
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  2. Artikel ; Online: Efficient and Easy Conversion of Human iPSCs into Functional Induced Microglia-like Cells.

    Lanfer, Jonas / Kaindl, Johanna / Krumm, Laura / Gonzalez Acera, Miguel / Neurath, Markus / Regensburger, Martin / Krach, Florian / Winner, Beate

    International journal of molecular sciences

    2022  Band 23, Heft 9

    Abstract: Current protocols converting human induced pluripotent stem cells (iPSCs) into induced microglia-like cells (iMGL) are either dependent on overexpression of transcription factors or require substantial experience in stem-cell technologies. Here, we ... ...

    Abstract Current protocols converting human induced pluripotent stem cells (iPSCs) into induced microglia-like cells (iMGL) are either dependent on overexpression of transcription factors or require substantial experience in stem-cell technologies. Here, we developed an easy-to-use two-step protocol to convert iPSCs into functional iMGL via: (1) highly efficient differentiation of hematopoietic progenitor cells (HPCs) from iPSCs, and (2) optimized maturation of HPCs to iMGL. A sequential harvesting approach led to an increased HPC yield. The protocol implemented a freezing step, thus allowing HPC biobanking and flexible timing of differentiation into iMGL. Our iMGL responded adequately to the inflammatory stimuli LPS, and iMGL RNAseq analysis matched those of other frequently used protocols. Comparing three different coating modalities, we increased the iMGL yield by culturing on uncoated glass surfaces, thereby retaining differentiation efficiency and functional hallmarks of iMGL. In summary, we provide a high-quality, easy-to-use protocol, rendering generation and functional studies on iMGL an accessible lab resource.
    Mesh-Begriff(e) Biological Specimen Banks ; Cell Differentiation ; Hematopoietic Stem Cells ; Humans ; Induced Pluripotent Stem Cells ; Microglia
    Sprache Englisch
    Erscheinungsdatum 2022-04-20
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23094526
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: The cellular microenvironment regulates CX3CR1 expression on CD8

    Pokharel, Jyoti / Shryki, Iman / Zwijnenburg, Anthonie J / Sandu, Ioana / Krumm, Laura / Bekiari, Christina / Avramov, Victor / Heinbäck, Rebecka / Lysell, Josefin / Eidsmo, Liv / Harris, Helena E / Gerlach, Carmen

    European journal of immunology

    2023  Band 54, Heft 1, Seite(n) e2350658

    Abstract: Expression levels of the chemokine receptor CX3CR1 serve as high-resolution marker delineating functionally distinct antigen-experienced T-cell states. The factors that influence CX3CR1 expression in T cells are, however, incompletely understood. Here, ... ...

    Abstract Expression levels of the chemokine receptor CX3CR1 serve as high-resolution marker delineating functionally distinct antigen-experienced T-cell states. The factors that influence CX3CR1 expression in T cells are, however, incompletely understood. Here, we show that in vitro priming of naïve CD8
    Mesh-Begriff(e) CD8-Positive T-Lymphocytes/metabolism ; Receptors, Chemokine/genetics ; Cellular Microenvironment ; Receptors, Antigen, T-Cell/metabolism ; CX3C Chemokine Receptor 1/metabolism
    Chemische Substanzen Receptors, Chemokine ; Receptors, Antigen, T-Cell ; CX3C Chemokine Receptor 1
    Sprache Englisch
    Erscheinungsdatum 2023-10-19
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.202350658
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 489: Hefte anzeigen Standort:
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  4. Artikel ; Online: Machine learning using multimodal and autonomic nervous system parameters predicts clinically apparent stroke-associated pneumonia in a development and testing study.

    Nelde, Alexander / Krumm, Laura / Arafat, Subhi / Hotter, Benjamin / Nolte, Christian H / Scheitz, Jan F / Klammer, Markus G / Krämer, Michael / Scheib, Franziska / Endres, Matthias / Meisel, Andreas / Meisel, Christian

    Journal of neurology

    2023  Band 271, Heft 2, Seite(n) 899–908

    Abstract: Background: Stroke-associated pneumonia (SAP) is a preventable determinant for poor outcome after stroke. Machine learning (ML) using large-scale clinical data warehouses may be able to predict SAP and identify patients for targeted interventions. The ... ...

    Abstract Background: Stroke-associated pneumonia (SAP) is a preventable determinant for poor outcome after stroke. Machine learning (ML) using large-scale clinical data warehouses may be able to predict SAP and identify patients for targeted interventions. The aim of this study was to develop a prediction model for identifying clinically apparent SAP using automated ML.
    Methods: The ML model used clinical and laboratory parameters along with heart rate (HR), heart rate variability (HRV), and blood pressure (BP) values obtained during the first 48 h after stroke unit admission. A logistic regression classifier was developed and internally validated with a nested-cross-validation (nCV) approach. For every shuffle, the model was first trained and validated with a fixed threshold for 0.9 sensitivity, then finally tested on the out-of-sample data and benchmarked against a widely validated clinical score (A2DS2).
    Results: We identified 2390 eligible patients admitted to two-stroke units at Charité between October 2020 and June 2023, of whom 1755 had all parameters available. SAP was diagnosed in 96/1755 (5.5%). Circadian profiles in HR, HRV, and BP metrics during the first 48 h after admission exhibited distinct differences between patients with SAP diagnosis vs. those without. CRP, mRS at admission, leukocyte count, high-frequency power in HRV, stroke severity at admission, sex, and diastolic BP were identified as the most informative ML features. We obtained an AUC of 0.91 (CI 0.88-0.95) for the ML model on the out-of-sample data in comparison to an AUC of 0.84 (CI 0.76-0.91) for the previously established A2DS2 score (p < 0.001). The ML model provided a sensitivity of 0.87 (CI 0.75-0.97) with a corresponding specificity of 0.82 (CI 0.78-0.85) which outperformed the A2DS2 score for multiple cutoffs.
    Conclusions: Automated, data warehouse-based prediction of clinically apparent SAP in the stroke unit setting is feasible, benefits from the inclusion of vital signs, and could be useful for identifying high-risk patients or prophylactic pneumonia management in clinical routine.
    Mesh-Begriff(e) Humans ; Risk Factors ; Prognosis ; Stroke/complications ; Stroke/diagnosis ; Pneumonia/diagnosis ; Pneumonia/etiology ; Machine Learning ; Autonomic Nervous System
    Sprache Englisch
    Erscheinungsdatum 2023-10-18
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 187050-6
    ISSN 1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    ISSN (online) 1432-1459
    ISSN 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
    DOI 10.1007/s00415-023-12031-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Ui II Zs.40: Hefte anzeigen Standort:
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  5. Artikel ; Online: Generation and characterization of an endogenously tagged SPG11-human iPSC line by CRISPR/Cas9 mediated knock-in.

    Krumm, Laura / Pozner, Tatyana / Kaindl, Johanna / Regensburger, Martin / Günther, Claudia / Turan, Soeren / Asadollahi, Reza / Rauch, Anita / Winner, Beate

    Stem cell research

    2021  Band 56, Seite(n) 102520

    Abstract: Pathogenic bi-allelic variants in the SPG11 gene result in rare motor neuron disorders such as Hereditary Spastic Paraplegia type 11, Charcot-Marie Tooth, and Juvenile Amyotrophic Lateral Sclerosis-5. The main challenge in SPG11-linked disease research ... ...

    Abstract Pathogenic bi-allelic variants in the SPG11 gene result in rare motor neuron disorders such as Hereditary Spastic Paraplegia type 11, Charcot-Marie Tooth, and Juvenile Amyotrophic Lateral Sclerosis-5. The main challenge in SPG11-linked disease research is the lack of antibodies against SPG11 encoded spatacsin. Here, we describe the CRISPR/Cas9 mediated generation and validation of an endogenously tagged SPG11- human iPSC line that contains an HA tag at the C-terminus of SPG11. The line exhibits multi-lineage differentiation potential and holds promise for studying the role of spatacsin and for the elucidation of SPG11-associated pathogenesis. Resource Table.
    Mesh-Begriff(e) CRISPR-Cas Systems/genetics ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Mutation ; Proteins/genetics ; Spastic Paraplegia, Hereditary/genetics
    Chemische Substanzen Proteins ; SPG11 protein, human
    Sprache Englisch
    Erscheinungsdatum 2021-08-26
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2021.102520
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients.

    Krumm, Laura / Pozner, Tatyana / Zagha, Naime / Coras, Roland / Arnold, Philipp / Tsaktanis, Thanos / Scherpelz, Kathryn / Davis, Marie Y / Kaindl, Johanna / Stolzer, Iris / Süß, Patrick / Khundadze, Mukhran / Hübner, Christian A / Riemenschneider, Markus J / Baets, Jonathan / Günther, Claudia / Jayadev, Suman / Rothhammer, Veit / Krach, Florian /
    Winkler, Jürgen / Winner, Beate / Regensburger, Martin

    Acta neuropathologica

    2024  Band 147, Heft 1, Seite(n) 28

    Abstract: Biallelic loss of SPG11 function constitutes the most frequent cause of complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration. While the impact of ... ...

    Abstract Biallelic loss of SPG11 function constitutes the most frequent cause of complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration. While the impact of neuroinflammation is an emerging and potentially treatable aspect in neurodegenerative diseases and leukodystrophies, the role of immune cells in SPG11-HSP patients is unknown. Here, we performed a comprehensive immunological characterization of SPG11-HSP, including examination of three human postmortem brain donations, immunophenotyping of patients' peripheral blood cells and patient-specific induced pluripotent stem cell-derived microglia-like cells (iMGL). We delineate a previously unknown role of innate immunity in SPG11-HSP. Neuropathological analysis of SPG11-HSP patient brain tissue revealed profound microgliosis in areas of neurodegeneration, downregulation of homeostatic microglial markers and cell-intrinsic accumulation of lipids and lipofuscin in IBA1
    Mesh-Begriff(e) Animals ; Mice ; Humans ; Spastic Paraplegia, Hereditary/genetics ; Spastic Paraplegia, Hereditary/pathology ; Neuroinflammatory Diseases ; Proteins/genetics ; Neurons/pathology ; Mutation
    Chemische Substanzen Proteins ; SPG11 protein, human ; SPG11 protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2024-02-02
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-023-02675-w
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  7. Artikel ; Online: Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia.

    Regensburger, Martin / Krumm, Laura / Schmidt, Manuel Alexander / Schmid, Andreas / Spatz, Imke Tabea / Marterstock, Dominique Cornelius / Kopp, Christoph / Kohl, Zacharias / Doerfler, Arnd / Karrasch, Thomas / Winner, Beate / Winkler, Jürgen

    Nutrients

    2022  Band 14, Heft 22

    Abstract: Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported ... ...

    Abstract Background: Pathogenic variants in SPG11 cause the most common autosomal recessive complicated hereditary spastic paraplegia. Besides the prototypical combination of spastic paraplegia with a thin corpus callosum, obesity has increasingly been reported in this multisystem neurodegenerative disease. However, a detailed analysis of the metabolic state is lacking.
    Methods: In order to characterize metabolic alterations, a cross-sectional analysis was performed comparing SPG11 patients (n = 16) and matched healthy controls (n = 16). We quantified anthropometric parameters, body composition as determined by bioimpedance spectroscopy, and serum metabolic biomarkers, and we measured hypothalamic volume by high-field MRI.
    Results: Compared to healthy controls, SPG11 patients exhibited profound changes in body composition, characterized by increased fat tissue index, decreased lean tissue index, and decreased muscle mass. The presence of lymphedema correlated with increased extracellular fluid. The serum levels of the adipokines leptin, resistin, and progranulin were significantly altered in SPG11 while adiponectin and C1q/TNF-related protein 3 (CTRP-3) were unchanged. MRI volumetry revealed a decreased hypothalamic volume in SPG11 patients.
    Conclusions: Body composition, adipokine levels, and hypothalamic volume are altered in SPG11. Our data indicate a link between obesity and hypothalamic neurodegeneration in SPG11 and imply that specific metabolic interventions may prevent obesity despite severely impaired mobility in SPG11.
    Mesh-Begriff(e) Humans ; Spastic Paraplegia, Hereditary/pathology ; Cross-Sectional Studies ; Neurodegenerative Diseases ; Mutation ; Obesity ; Proteins
    Chemische Substanzen SPG11 protein, human ; Proteins
    Sprache Englisch
    Erscheinungsdatum 2022-11-13
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu14224803
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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