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Article ; Online: Mouse Models of Kidney Fibrosis.

Kramann, Rafael / Menzel, Sylvia

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2299, Page(s) 323–338

Abstract: Chronic kidney disease (CKD) affects over 10% of the worldwide population and kidney fibrosis is a main driver of CKD and considered a therapeutic target. The mechanisms leading to kidney fibrosis are highly complexed and can be best studied in rodent ... ...

Abstract	Chronic kidney disease (CKD) affects over 10% of the worldwide population and kidney fibrosis is a main driver of CKD and considered a therapeutic target. The mechanisms leading to kidney fibrosis are highly complexed and can be best studied in rodent models. Here we describe the most commonly used kidney fibrosis models in mice, the unilateral ureteral obstruction (UUO) model and the ischemia reperfusion injury (IRI) model. Both models are easy to learn and can be applied in animals of different age, sex, and strain.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Disease Models, Animal ; Female ; Fibrosis ; Humans ; Kidney/metabolism ; Kidney/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury/metabolism ; Reperfusion Injury/pathology ; Ureteral Obstruction/metabolism ; Ureteral Obstruction/pathology
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-05-24
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1382-5_22
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Article: Disturbance and indirect effects of climate warming support a plant invader in mountains

Haider, Sylvia / Palm, Sebastian / Bruelheide, Helge / de Villemereuil, Pierre / Menzel, Annette / Lachmuth, Susanne

Oikos. 2022 Apr., v. 2022, no. 4

2022

Abstract: Climate warming and increased disturbance (resulting from intensified land use) are expected to enhance the invasibility of plant communities and the performance of exotic species also at high elevations, and thus pose additional threats to mountain ... ...

Abstract	Climate warming and increased disturbance (resulting from intensified land use) are expected to enhance the invasibility of plant communities and the performance of exotic species also at high elevations, and thus pose additional threats to mountain ecosystems. The invasion success of introduced genotypes will also depend on their degree of pre‐adaption to high elevation climatic conditions, which may vary intra‐specifically across source populations. For populations currently spreading in the lowlands, climate warming might reduce the climatic distance to high‐elevation sites and thus remove a barrier to upwards spread. Here, we investigated the various facets of mountain invasions in a single, integrative experimental study. We applied a community transplant approach between high‐ and low‐elevation sites in the European Alps to address effects of climate warming and disturbance through land use on community invasibility and the performance of the exotic species Senecio inaequidens, a potential future plant invader in the Alps. Additionally, the transplant sites served as common gardens to test the influence of climatic pre‐adaptation to current (high site) and future (low site) climatic conditions on the performance of S. inaequidens in the transplanted communities. The 16 invasive central and western European S. inaequidens source population locations covered a wide geographic range, and thus a wide amplitude of climatic distances and presumed pre‐adaptation to our gardens. Our results attest to a strong effect of disturbance, which increased community invasibility, and promoted the performance of the exotic species. Contrary to our expectation, experimentally induced climate warming did not increase community invasibility. However, the performance of the S. inaequidens populations was positively related to their pre‐adaptation to the climatic conditions of our common gardens. Climate warming might thus promote the invasion of exotic species by reducing the climatic distance between mountain ranges and locations of potential source populations.
Keywords	Senecio inaequidens ; altitude ; colonizing ability ; geographical distribution ; introduced species ; land use
Language	English
Dates of publication	2022-04
Publishing place	Blackwell Publishing Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	207359-6
ISSN	0030-1299
ISSN	0030-1299
DOI	10.1111/oik.08783
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen.

Li, Zhijian / Kuppe, Christoph / Ziegler, Susanne / Cheng, Mingbo / Kabgani, Nazanin / Menzel, Sylvia / Zenke, Martin / Kramann, Rafael / Costa, Ivan G

Nature communications

2021 Volume 12, Issue 1, Page(s) 6386

Abstract: A major drawback of single-cell ATAC-seq (scATAC-seq) is its sparsity, i.e., open chromatin regions with no reads due to loss of DNA material during the scATAC-seq protocol. Here, we propose scOpen, a computational method based on regularized non- ... ...

Abstract	A major drawback of single-cell ATAC-seq (scATAC-seq) is its sparsity, i.e., open chromatin regions with no reads due to loss of DNA material during the scATAC-seq protocol. Here, we propose scOpen, a computational method based on regularized non-negative matrix factorization for imputing and quantifying the open chromatin status of regulatory regions from sparse scATAC-seq experiments. We show that scOpen improves crucial downstream analysis steps of scATAC-seq data as clustering, visualization, cis-regulatory DNA interactions, and delineation of regulatory features. We demonstrate the power of scOpen to dissect regulatory changes in the development of fibrosis in the kidney. This identifies a role of Runx1 and target genes by promoting fibroblast to myofibroblast differentiation driving kidney fibrosis.
MeSH term(s)	Chromatin/metabolism ; DNA/metabolism ; Sequence Analysis, DNA/methods ; Sequence Analysis, DNA/standards ; Single-Cell Analysis/methods
Chemical Substances	Chromatin ; DNA (9007-49-2)
Language	English
Publishing date	2021-11-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-26530-2
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Article ; Online: Chromatin-accessibility estimation from single-cell ATAC-seq data with scOpen

Zhijian Li / Christoph Kuppe / Susanne Ziegler / Mingbo Cheng / Nazanin Kabgani / Sylvia Menzel / Martin Zenke / Rafael Kramann / Ivan G. Costa

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 14

Abstract: scATAC-Seq yields data that is extremely sparse. Here, the authors present a computationally efficient imputation method called scOpen that improves the downstream analyses of scATAC-Seq data and use it to identify transcriptional regulators of kidney ... ...

Abstract	scATAC-Seq yields data that is extremely sparse. Here, the authors present a computationally efficient imputation method called scOpen that improves the downstream analyses of scATAC-Seq data and use it to identify transcriptional regulators of kidney fibrosis.
Keywords	Science ; Q
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High Concordance of Different Assays in the Determination of Homologous Recombination Deficiency-Associated Genomic Instability in Ovarian Cancer.

Pfarr, Nicole / von Schwarzenberg, Karin / Zocholl, Dario / Merkelbach-Bruse, Sabine / Siemanowski, Janna / Mayr, Eva-Maria / Herold, Sylvia / Kleo, Karsten / Heukamp, Lukas C / Willing, Eva-Maria / Menzel, Michael / Lehmann, Ulrich / Bartels, Stephan / Chakraborty, Shounak / Baretton, Gustavo / Demes, Melanie C / Döring, Claudia / Kazdal, Daniel / Budczies, Jan /

Rad, Roland / Wild, Peter / Christinat, Yann / McKee, Thomas / Schirmacher, Peter / Horst, David / Büttner, Reinhard / Stenzinger, Albrecht / Sehouli, Jalid / Vollbrecht, Claudia / Hummel, Michael / Braicu, Elena I / Weichert, Wilko

JCO precision oncology

2024 Volume 8, Page(s) e2300348

Abstract: Purpose: Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis of biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency ...

Abstract	Purpose: Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis of biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency (HRD). The test that is most often used for the detection of HRD in clinical studies is the Myriad myChoice assay. However, other assays can also be used to assess biomarkers, which are indicative of HRD, genomic instability (GI), and Methods: DNA from HGSOC samples was extracted from formalin-fixed paraffin-embedded tissue blocks of cases previously run with the Myriad myChoice assay, and GI was measured by multiple molecular assays (CytoSNP, AmoyDx, Illumina TSO500 HRD, OncoScan, NOGGO GISv1, QIAseq HRD Panel and whole genome sequencing), applying different bioinformatics algorithms. Results: Application of different assays to assess GI, including Myriad myChoice, revealed high concordance of the generated scores ranging from very substantial to nearly perfect fit, depending on the assay and bioinformatics pipelines applied. Interlaboratory comparison of assays also showed high concordance of GI scores. Conclusion: Assays for GI assessment not only show a high concordance with each other but also in correlation with Myriad myChoice. Thus, almost all of the assays included here can be used effectively to assess HRD-associated GI in the clinical setting. This is important as PARPi treatment on the basis of these tests is compliant with European Medicines Agency approvals, which are methodologically not test-bound.
MeSH term(s)	Humans ; Female ; BRCA1 Protein/genetics ; Mutation ; BRCA2 Protein/genetics ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/drug therapy ; Genomic Instability/genetics ; Homologous Recombination/genetics
Chemical Substances	BRCA1 protein, human ; BRCA1 Protein ; BRCA2 protein, human ; BRCA2 Protein
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.23.00348
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Article ; Online: Platelet-instructed SPP1

Cell reports

2023 Volume 42, Issue 2, Page(s) 112131

Abstract: Fibrosis represents the common end stage of chronic organ injury independent of the initial insult, destroying tissue architecture and driving organ failure. Here we discover a population of profibrotic macrophages marked by expression of Spp1, Fn1, and ... ...

Abstract	Fibrosis represents the common end stage of chronic organ injury independent of the initial insult, destroying tissue architecture and driving organ failure. Here we discover a population of profibrotic macrophages marked by expression of Spp1, Fn1, and Arg1 (termed Spp1 macrophages), which expands after organ injury. Using an unbiased approach, we identify the chemokine (C-X-C motif) ligand 4 (CXCL4) to be among the top upregulated genes during profibrotic Spp1 macrophage differentiation. In vitro and in vivo studies show that loss of Cxcl4 abrogates profibrotic Spp1 macrophage differentiation and ameliorates fibrosis after both heart and kidney injury. Moreover, we find that platelets, the most abundant source of CXCL4 in vivo, drive profibrotic Spp1 macrophage differentiation. Single nuclear RNA sequencing with ligand-receptor interaction analysis reveals that macrophages orchestrate fibroblast activation via Spp1, Fn1, and Sema3 crosstalk. Finally, we confirm that Spp1 macrophages expand in both human chronic kidney disease and heart failure.
MeSH term(s)	Humans ; Fibrosis ; Ligands ; Macrophages/metabolism ; Myofibroblasts/metabolism ; Osteopontin ; Platelet Factor 4/genetics ; Platelet Factor 4/metabolism
Chemical Substances	Ligands ; Osteopontin (106441-73-0) ; Platelet Factor 4 (37270-94-3) ; SPP1 protein, human ; PF4 protein, human
Language	English
Publishing date	2023-02-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112131
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Article ; Online: Role of the podocyte in proteinuria.

Menzel, Sylvia / Moeller, Marcus J

Pediatric nephrology (Berlin, Germany)

2010 Volume 26, Issue 10, Page(s) 1775–1780

Abstract: In recent years, the podocyte, with its elaborate cytoarchitecture and slit diaphragm, has been the focus of extensive research, yet its precise role in the glomerular filtration barrier is still debated. There are puzzling observations indicating that a ...

Abstract	In recent years, the podocyte, with its elaborate cytoarchitecture and slit diaphragm, has been the focus of extensive research, yet its precise role in the glomerular filtration barrier is still debated. There are puzzling observations indicating that a comprehensive mechanistic model for glomerular filtration is still necessary. There is no doubt that podocytes are essential for glomerular filtration barrier integrity. However, most albumin never reaches the podocyte because it is prevented from entering the glomerular filter at the endothelium level. Another puzzling observation is that the glomerular filter never clogs despite its high load of several kilograms of plasma proteins per day. Recently, we proposed a novel model in which an electrical potential difference is generated across the glomerular filtration barrier by filtration. The model offers novel potential solutions to some of the riddles regarding the glomerular filter.
MeSH term(s)	Animals ; Endothelium/metabolism ; Endothelium/pathology ; Endothelium/physiopathology ; Glomerular Filtration Barrier ; Humans ; Kidney/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Kidney Glomerulus/physiopathology ; Podocytes/pathology ; Proteinuria/metabolism ; Proteinuria/pathology ; Proteinuria/physiopathology ; Serum Albumin/metabolism
Chemical Substances	Serum Albumin
Language	English
Publishing date	2010-12-24
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-010-1725-5
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Article ; Online: Differences in appearance-related commentary, body dissatisfaction, and eating disturbance among college women of varying weight groups.

Herbozo, Sylvia / Menzel, Jessie E / Thompson, J Kevin

Eating behaviors

2013 Volume 14, Issue 2, Page(s) 204–206

Abstract: This study examined appearance-related commentary, body dissatisfaction, and eating disturbance in 924 undergraduate females. Significant group differences were found in type of appearance-related commentary received across weight groups. Overweight and ... ...

Abstract	This study examined appearance-related commentary, body dissatisfaction, and eating disturbance in 924 undergraduate females. Significant group differences were found in type of appearance-related commentary received across weight groups. Overweight and obese women experienced negative weight and shape-related comments at greater frequencies and positive weight and shape-related comments at lower frequencies compared to underweight and normal weight women. A higher frequency of positive weight and shape-related commentary was associated with less body dissatisfaction for all women and less shape and weight concerns for obese women. These findings suggest that the weight status of young women likely influences the appearance-related commentary that they receive and the manner in which such commentary affects their body image and eating behaviors.
MeSH term(s)	Adolescent ; Adult ; Body Image ; Body Weight ; Feeding Behavior/psychology ; Feeding and Eating Disorders/psychology ; Female ; Humans ; Ideal Body Weight ; Obesity/psychology ; Overweight/psychology ; Personal Satisfaction ; Social Environment ; Students/psychology ; Thinness/psychology ; Universities ; Women/psychology ; Young Adult
Language	English
Publishing date	2013-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2073366-5
ISSN	1873-7358 ; 1471-0153
ISSN (online)	1873-7358
ISSN	1471-0153
DOI	10.1016/j.eatbeh.2013.01.013
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Article: Differences in appearance-related commentary, body dissatisfaction, and eating disturbance among college women of varying weight groups

Herbozo, Sylvia / Menzel, Jessie E / Thompson, J. Kevin

Eating behaviors. 2013 Apr., v. 14, no. 2

2013

Abstract	This study examined appearance-related commentary, body dissatisfaction, and eating disturbance in 924 undergraduate females. Significant group differences were found in type of appearance-related commentary received across weight groups. Overweight and obese women experienced negative weight and shape-related comments at greater frequencies and positive weight and shape-related comments at lower frequencies compared to underweight and normal weight women. A higher frequency of positive weight and shape-related commentary was associated with less body dissatisfaction for all women and less shape and weight concerns for obese women. These findings suggest that the weight status of young women likely influences the appearance-related commentary that they receive and the manner in which such commentary affects their body image and eating behaviors.
Keywords	body image ; eating habits ; females ; overweight ; underweight ; women
Language	English
Dates of publication	2013-04
Size	p. 204-206.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2073366-5
ISSN	1471-0153
ISSN	1471-0153
DOI	10.1016/j.eatbeh.2013.01.013
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Article ; Online: Deep Learning-Based Segmentation and Quantification in Experimental Kidney Histopathology.

Bouteldja, Nassim / Klinkhammer, Barbara M / Bülow, Roman D / Droste, Patrick / Otten, Simon W / Freifrau von Stillfried, Saskia / Moellmann, Julia / Sheehan, Susan M / Korstanje, Ron / Menzel, Sylvia / Bankhead, Peter / Mietsch, Matthias / Drummer, Charis / Lehrke, Michael / Kramann, Rafael / Floege, Jürgen / Boor, Peter / Merhof, Dorit

Journal of the American Society of Nephrology : JASN

2020 Volume 32, Issue 1, Page(s) 52–68

Abstract: Background: Nephropathologic analyses provide important outcomes-related data in experiments with the animal models that are essential for understanding kidney disease pathophysiology. Precision medicine increases the demand for quantitative, unbiased, ... ...

Abstract	Background: Nephropathologic analyses provide important outcomes-related data in experiments with the animal models that are essential for understanding kidney disease pathophysiology. Precision medicine increases the demand for quantitative, unbiased, reproducible, and efficient histopathologic analyses, which will require novel high-throughput tools. A deep learning technique, the convolutional neural network, is increasingly applied in pathology because of its high performance in tasks like histology segmentation. Methods: We investigated use of a convolutional neural network architecture for accurate segmentation of periodic acid-Schiff-stained kidney tissue from healthy mice and five murine disease models and from other species used in preclinical research. We trained the convolutional neural network to segment six major renal structures: glomerular tuft, glomerulus including Bowman's capsule, tubules, arteries, arterial lumina, and veins. To achieve high accuracy, we performed a large number of expert-based annotations, 72,722 in total. Results: Multiclass segmentation performance was very high in all disease models. The convolutional neural network allowed high-throughput and large-scale, quantitative and comparative analyses of various models. In disease models, computational feature extraction revealed interstitial expansion, tubular dilation and atrophy, and glomerular size variability. Validation showed a high correlation of findings with current standard morphometric analysis. The convolutional neural network also showed high performance in other species used in research-including rats, pigs, bears, and marmosets-as well as in humans, providing a translational bridge between preclinical and clinical studies. Conclusions: We developed a deep learning algorithm for accurate multiclass segmentation of digital whole-slide images of periodic acid-Schiff-stained kidneys from various species and renal disease models. This enables reproducible quantitative histopathologic analyses in preclinical models that also might be applicable to clinical studies.
MeSH term(s)	Algorithms ; Animals ; Deep Learning ; Diagnosis, Computer-Assisted ; Disease Models, Animal ; Image Processing, Computer-Assisted/methods ; Kidney/physiopathology ; Kidney Diseases/pathology ; Kidney Glomerulus/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neural Networks, Computer ; Pattern Recognition, Automated ; Periodic Acid/chemistry ; Reproducibility of Results ; Schiff Bases ; Translational Research, Biomedical
Chemical Substances	Schiff Bases ; Periodic Acid (10450-60-9)
Language	English
Publishing date	2020-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2020050597
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