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1دورية أكاديمية
المؤلفون: Pierpont, Elizabeth I., Bennett, Anton M., Schoyer, Lisa, Stronach, Beth, Anschutz, April, Borrie, Sarah C., Briggs, Benjamin, Burkitt‐Wright, Emma, Castel, Pau, Cirstea, Ion C., Andelfinger, Gregor
المساهمون: Pierpont, Elizabeth I., Bennett, Anton M., Schoyer, Lisa, Stronach, Beth, Anschutz, April, Borrie, Sarah C., Briggs, Benjamin, Burkitt‐Wright, Emma, Castel, Pau, Cirstea, Ion C., Andelfinger, Gregor
الوصف: Germline pathogenic variants in the RAS/mitogen‐activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes. RASopathies constitute a wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies in nearly all the major body systems. With increasing global recognition of these conditions, the 8th International RASopathies Symposium spotlighted global perspectives on clinical care and research, including strategies for building international collaborations and developing diverse patient cohorts in anticipation of interventional trials. This biannual meeting, organized by RASopathies Network, was held in a hybrid virtual/in‐person format. The agenda featured emerging discoveries and case findings as well as progress in preclinical and therapeutic pipelines. Stakeholders including basic scientists, clinician‐scientists, practitioners, industry representatives, patients, and family advocates gathered to discuss cutting edge science, recognize current gaps in knowledge, and hear from people with RASopathies about the experience of daily living. Presentations by RASopathy self‐advocates and early‐stage investigators were featured throughout the program to encourage a sustainable, diverse, long‐term research and advocacy partnership focused on improving health and bringing treatments to people with RASopathies. ; BioMarin Pharmaceutical https://doi.org/10.13039/100008484Test ; Boehringer Ingelheim https://doi.org/10.13039/100001003Test ; Children's Hospital Colorado https://doi.org/10.13039/100007180Test ; National Cancer Institute https://doi.org/10.13039/100000054Test ; National Center for Advancing Translational Sciences https://doi.org/10.13039/100006108Test ; Revolution Medicines https://doi.org/10.13039/100019364Test ; Children's Tumor Foundation https://doi.org/10.13039/100001545Test ; National Institutes of Health https://doi.org/10.13039/100000002Test ; Deutsche Forschungsgemeinschaft ...
الإتاحة: https://doi.org/10.1002/ajmg.a.63477Test
https://resolver.sub.uni-goettingen.de/purl?gro-2/139162Test -
2دورية أكاديمية
المؤلفون: Tschaffon, Miriam E. A., Reber, Stefan O., Schoppa, Astrid, Nandi, Sayantan, Cirstea, Ion C., Aszodi, Attila, Ignatius, Anita, Haffner-Luntzer, Melanie
مصطلحات موضوعية: Transdifferentiation, Cartilage to bone transformation, Endochondral ossification, Chondrocyte, In vitro assay, DDC 610 / Medicine & health, Osteogenesis, Chondrocytes, Fracture healing, Knochenbildung, Knorpelzelle, Frakturheilung
الوصف: Purpose Endochondral ossification, which involves transdifferentiation of chondrocytes into osteoblasts, is an important process involved in the development and postnatal growth of most vertebrate bones as well as in bone fracture healing. To study the basic molecular mechanisms of this process, a robust and easy-to-use in vitro model is desirable. Therefore, we aimed to develop a standardized in vitro assay for the transdifferentiation of chondrogenic cells towards the osteogenic lineage. Methods Murine chondrogenic ATDC5 cells were differentiated into the chondrogenic lineage for seven days and subsequently differentiated towards the osteogenic direction. Gene expression analysis of pluripotency, as well as chondrogenic and osteogenic markers, cell–matrix staining, and immunofluorescent staining, were performed to assess the differentiation. In addition, the effects of Wnt3a and lipopolysaccharides (LPS) on the transdifferentiation were tested by their addition to the osteogenic differentiation medium. Results Following osteogenic differentiation, chondrogenically pe-differentiated cells displayed the expression of pluripotency and osteogenic marker genes as well as alkaline phosphatase activity and a mineralized matrix. Co-expression of Col2a1 and Col1a1 after one day of osteogenic differentiation indicated that osteogenic cells had differentiated from chondrogenic cells. Wnt3a increased and LPS decreased transdifferentiation towards the osteogenic lineage. Conclusion We successfully established a rapid, standardized in vitro assay for the transdifferentiation of chondrogenic cells into osteogenic cells, which is suitable for testing the effects of different compounds on this cellular process. ; publishedVersion
وصف الملف: application/pdf
العلاقة: https://static-content.springer.com/esm/art%3A10.1007%2Fs12020-021-02853-4/MediaObjects/12020_2021_2853_MOESM1_ESM.aviTest; https://static-content.springer.com/esm/art%3A10.1007%2Fs12020-021-02853-4/MediaObjects/12020_2021_2853_MOESM2_ESM.aviTest; http://dx.doi.org/10.18725/OPARU-49749Test; https://oparu.uni-ulm.de/xmlui/123456789/49825Test; http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-49825-1Test
الإتاحة: https://doi.org/10.18725/OPARU-49749Test
https://oparu.uni-ulm.de/xmlui/123456789/49825Test
http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-49825-1Test -
3دورية أكاديمية
المؤلفون: Ahmad, Mubashir, Krüger, Benjamin Thilo, Kroll, Torsten, Vettorazzi, Sabine, Dorn, Ann-Kristin, Mengele, Florian, Lee, Sooyeon, Nandi, Sayantan, Yilmaz, Dilay, Stolz, Miriam, Tangudu, Naveen Kumar, Carro Vázquez, David, Pachmayr, Johanna, Cirstea, Ion C., Spasić Vujić, Maja, Ploubidou, Aspasia, Ignatius, Anita, Tuckermann, Jan
مصطلحات موضوعية: DDC 570 / Life sciences, DDC 610 / Medicine & health, Bone, Metabolic bone disease, Knochen
الوصف: Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis, a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5 (Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by siRNA, genetic deletion using the Cre-loxP system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing. ; publishedVersion
وصف الملف: application/pdf
العلاقة: https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM1_ESM.docxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM2_ESM.xlsxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM3_ESM.xlsxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM4_ESM.xlsxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM5_ESM.xlsxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM6_ESM.xlsxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM7_ESM.xlsxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM8_ESM.xlsxTest; https://static-content.springer.com/esm/art%3A10.1038%2Fs41413-022-00195-z/MediaObjects/41413_2022_195_MOESM9_ESM.xlsxTest; http://dx.doi.org/10.18725/OPARU-48853Test; https://oparu.uni-ulm.de/xmlui/123456789/48929Test; http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-48929-5Test
الإتاحة: https://doi.org/10.18725/OPARU-48853Test
https://oparu.uni-ulm.de/xmlui/123456789/48929Test
http://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-48929-5Test -
4دورية أكاديمية
المؤلفون: Pierpont, Elizabeth I., Bennett, Anton M., Schoyer, Lisa, Stronach, Beth, Anschutz, April, Borrie, Sarah C., Briggs, Benjamin, Burkitt‐Wright, Emma, Castel, Pau, Cirstea, Ion C., Draaisma, Fieke, Ellis, Michelle, Fear, Vanessa S., Frone, Megan N., Flex, Elisabetta, Gelb, Bruce D., Green, Tamar, Gripp, Karen W., Khoshkhoo, Sattar, Kieran, Mark W.
المصدر: American Journal of Medical Genetics. Part A; Apr2024, Vol. 194 Issue 4, p1-11, 11p
مستخلص: Germline pathogenic variants in the RAS/mitogen‐activated protein kinase (MAPK) signaling pathway are the molecular cause of RASopathies, a group of clinically overlapping genetic syndromes. RASopathies constitute a wide clinical spectrum characterized by distinct facial features, short stature, predisposition to cancer, and variable anomalies in nearly all the major body systems. With increasing global recognition of these conditions, the 8th International RASopathies Symposium spotlighted global perspectives on clinical care and research, including strategies for building international collaborations and developing diverse patient cohorts in anticipation of interventional trials. This biannual meeting, organized by RASopathies Network, was held in a hybrid virtual/in‐person format. The agenda featured emerging discoveries and case findings as well as progress in preclinical and therapeutic pipelines. Stakeholders including basic scientists, clinician‐scientists, practitioners, industry representatives, patients, and family advocates gathered to discuss cutting edge science, recognize current gaps in knowledge, and hear from people with RASopathies about the experience of daily living. Presentations by RASopathy self‐advocates and early‐stage investigators were featured throughout the program to encourage a sustainable, diverse, long‐term research and advocacy partnership focused on improving health and bringing treatments to people with RASopathies. [ABSTRACT FROM AUTHOR]
: Copyright of American Journal of Medical Genetics. Part A is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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5دورية أكاديمية
المؤلفون: Tschaffon-Müller, Miriam Eva Angelica, Reber, Stefan O., Schoppa, Astrid, Nandi, Sayantan, Cirstea, Ion C., Aszodi, Attila, Ignatius, Anita, Haffner-Luntzer, Melanie
المصدر: http://lobid.org/resources/99370673530106441Test#!, 75(1):266-275.
مصطلحات موضوعية: In vitro assay, Osteogenesis [MeSH], Cartilage to bone transformation, Fracture healing, Osteoblasts [MeSH], Cell Differentiation [MeSH], Animals [MeSH], Endochondral ossification, Original Article, Mice [MeSH], Cell Transdifferentiation [MeSH], Transdifferentiation, Chondrocyte, Cells, Cultured [MeSH], Chondrocytes/metabolism [MeSH], Chondrogenesis/genetics [MeSH]
الوصف: Purpose!#!Endochondral ossification, which involves transdifferentiation of chondrocytes into osteoblasts, is an important process involved in the development and postnatal growth of most vertebrate bones as well as in bone fracture healing. To study the basic molecular mechanisms of this process, a robust and easy-to-use in vitro model is desirable. Therefore, we aimed to develop a standardized in vitro assay for the transdifferentiation of chondrogenic cells towards the osteogenic lineage.!##!Methods!#!Murine chondrogenic ATDC5 cells were differentiated into the chondrogenic lineage for seven days and subsequently differentiated towards the osteogenic direction. Gene expression analysis of pluripotency, as well as chondrogenic and osteogenic markers, cell-matrix staining, and immunofluorescent staining, were performed to assess the differentiation. In addition, the effects of Wnt3a and lipopolysaccharides (LPS) on the transdifferentiation were tested by their addition to the osteogenic differentiation medium.!##!Results!#!Following osteogenic differentiation, chondrogenically pe-differentiated cells displayed the expression of pluripotency and osteogenic marker genes as well as alkaline phosphatase activity and a mineralized matrix. Co-expression of Col2a1 and Col1a1 after one day of osteogenic differentiation indicated that osteogenic cells had differentiated from chondrogenic cells. Wnt3a increased and LPS decreased transdifferentiation towards the osteogenic lineage.!##!Conclusion!#!We successfully established a rapid, standardized in vitro assay for the transdifferentiation of chondrogenic cells into osteogenic cells, which is suitable for testing the effects of different compounds on this cellular process.
العلاقة: https://repository.publisso.de/resource/frl:6444296Test; https://doi.org/10.1007/s12020-021-02853-4Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763722Test/
الإتاحة: https://doi.org/10.1007/s12020-021-02853-4Test
https://repository.publisso.de/resource/frl:6444296Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763722Test/ -
6دورية أكاديمية
المؤلفون: Cirstea, Ion C., Moll, Herwig P., Tuckermann, Jan
المصدر: Trends in Cell Biology ; volume 33, issue 7, page 594-604 ; ISSN 0962-8924
مصطلحات موضوعية: Cell Biology
الإتاحة: https://doi.org/10.1016/j.tcb.2022.11.002Test
https://api.elsevier.com/content/article/PII:S0962892422002537?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0962892422002537?httpAccept=text/plainTest -
7دورية أكاديمية
المصدر: Pharmaceuticals 12(2), 70 (2019). doi:10.3390/ph12020070 special issue: "Special Issue "Iron as Therapeutic Targets in Human Diseases" / Special Issue Editors: Prof. Dr. Paolo Arosio, Guest Editor; Dr. Maura Poli, Guest Editor; Dr. Raffaella Gozzelino, Guest Editor"
جغرافية الموضوع: DE
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/pmid:31067696; info:eu-repo/semantics/altIdentifier/wos/WOS:000477028700025; info:eu-repo/semantics/altIdentifier/issn/1424-8247; https://publications.rwth-aachen.de/record/785961Test; https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-241268%22Test
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8دورية أكاديمية
المؤلفون: Motta, Marialetizia, Fidan, Miray, Bellacchio, Emanuele, Pantaleoni, Francesca, Schneider-Heieck, Konstantin, Coppola, Simona, Borck, Guntram, Salviati, Leonardo, Zenker, Martin, Cirstea, Ion C, Tartaglia, Marco
المساهمون: Associazione Italiana per la Ricerca sul Cancro, Ministero della Salute, Federal Ministry of Education and Research
المصدر: Human Molecular Genetics ; volume 28, issue 6, page 1007-1022 ; ISSN 0964-6906 1460-2083
الإتاحة: https://doi.org/10.1093/hmg/ddy412Test
http://academic.oup.com/hmg/article-pdf/28/6/1007/28011141/ddy412.pdfTest -
9دورية أكاديمية
المؤلفون: Nakhaei-Rad, Saeideh, Nakhaeizadeh, Hossein, Kordes, Claus, Cirstea, Ion C., Schmick, Malte, Dvorsky, Radovan, Bastiaens, Philippe I.H., Häussinger, Dieter, Ahmadian, Mohammad Reza
المصدر: Journal of Biological Chemistry ; volume 290, issue 25, page 15892-15903 ; ISSN 0021-9258
مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry
الإتاحة: https://doi.org/10.1074/jbc.m115.640607Test
https://api.elsevier.com/content/article/PII:S002192582035081X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S002192582035081X?httpAccept=text/plainTest -
10دورية أكاديمية
المؤلفون: Zhang, Si-Cai, Gremer, Lothar, Heise, Henrike, Janning, Petra, Shymanets, Aliaksei, Cirstea, Ion C., Krause, Eberhard, Nürnberg, Bernd, Ahmadian, Mohammad Reza
المصدر: PLOS ONE, 9(7):e102425
مصطلحات موضوعية: Detergents, Liposomes, Guanine nucleotide exchange factors, Sedimentation, Lipids, Cell membranes, Guanosine triphosphatase, Insects
الوصف: Small Rho GTPases are well known to regulate a variety of cellular processes by acting as molecular switches. The regulatory function of Rho GTPases is critically dependent on their posttranslational modification at the carboxyl terminus by isoprenylation and association with proper cellular membranes. Despite numerous studies, the mechanisms of recycling and functional integration of Rho GTPases at the biological membranes are largely unclear. In this study, prenylated human Rac1, a prominent member of the Rho family, was purified in large amount from baculovirus-infected Spodoptera frugiperda insect cells using a systematic detergent screening. In contrast to non-prenylated human Rac1 purified from Escherichia coli, prenylated Rac1 from insect cells was able to associate with synthetic liposomes and to bind Rho-specific guanine nucleotide dissociation inhibitor 1 (GDI1). Subsequent liposome reconstitution experiments revealed that GDI1 efficiently extracts Rac1 from liposomes preferentially in the inactive GDP-bound state. The extraction was prevented when Rac1 was activated to its GTP-bound state by Rac-specific guanine nucleotide exchange factors (GEFs), such as Vav2, Dbl, Tiam1, P-Rex1 and TrioN, and bound by the downstream effector Pak1. We found that dissociation of Rac1-GDP from its complex with GDI1 strongly correlated with two distinct activities of especially Dbl and Tiam1, including liposome association and the GDP/GTP exchange. Taken together, our results provided first detailed insights into the advantages of the in vitro liposome-based reconstitution system to study both the integration of the signal transducing protein complexes and the mechanisms of regulation and signaling of small GTPases at biological membranes.
العلاقة: https://repository.publisso.de/resource/frl:6404830Test; http://dx.doi.org/10.1371/journal.pone.0102425Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094549Test/; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102425#s5Test
الإتاحة: https://doi.org/10.1371/journal.pone.0102425Test
https://repository.publisso.de/resource/frl:6404830Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094549Test/
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102425#s5Test